Small Molecule Inhibitors of Human Papillomavirus: A Review of Research from 1997 to 2021
- Authors: Duncan C.1, Gunosewoyo H.2, Mocerino M.1, Payne A.1
-
Affiliations:
- School of Molecular and Life Sciences, Curtin University
- Curtin Medical School, Curtin University
- Issue: Vol 31, No 33 (2024)
- Pages: 5308-5350
- Section: Anti-Infectives and Infectious Diseases
- URL: https://hum-ecol.ru/0929-8673/article/view/645051
- DOI: https://doi.org/10.2174/0929867331666230713165407
- ID: 645051
Cite item
Full Text
Abstract
:Human papillomavirus (HPV) infections are the cause of warts, lesions and cancer, with different types of HPV causing different symptoms. HPV infections are the primary cause of cervical cancer. There are over 220 different types of HPV, and only nine of these can currently be vaccinated. There is a need to treat these viral infections without just treating the symptoms of the infection, as is currently the main method. There is a wide range of small molecules that have been used to inhibit various stages of the HPV infectious cycle. This review examined 132 small molecules from 121 studies that specifically target aspects of HPV infections. HPV DNA encodes for six early genes (E1 to E7, skipping E3) and two late genes (L1 and L2). According to the results, these targets for small molecule inhibitors fall into three categories: those targeting E1 and E2, targeting E6 and E7 and, finally, targeting L1 and L2. Inhibitors of E6 and E7 are the most widely studied targets, with the majority of HPV inhibition in this area. While compounds targeting both E1/E2 and E6/E7 have made it to clinical trials, there has been no significant advancement on the topic.
About the authors
Caitlin Duncan
School of Molecular and Life Sciences, Curtin University
Email: info@benthamscience.net
Hendra Gunosewoyo
Curtin Medical School, Curtin University
Email: info@benthamscience.net
Mauro Mocerino
School of Molecular and Life Sciences, Curtin University
Author for correspondence.
Email: info@benthamscience.net
Alan Payne
School of Molecular and Life Sciences, Curtin University
Email: info@benthamscience.net
References
- Van Doorslaer, K.; Tan, Q.; Xirasagar, S.; Bandaru, S.; Gopalan, V.; Mohamoud, Y.; Huyen, Y.; McBride, A.A. The Papillomavirus Episteme: a central resource for papillomavirus sequence data and analysis. Nucleic Acids Res., 2013, 41(Database issue), D571-D578. PMID: 23093593
- Arroyo, L.S. Utrotning av HPV och livmoderhalscancer. , 2021. Available from: https://www.hpvcenter.se/=
- Van Doorslaer, K. Evolution of the papillomaviridae. Virology, 2013, 445(1-2), 11-20. doi: 10.1016/j.virol.2013.05.012 PMID: 23769415
- Smith, L.; Angarone, M.P. Sexually transmitted infections. Urol. Clin. North Am., 2015, 42(4), 507-518. doi: 10.1016/j.ucl.2015.06.004 PMID: 26475947
- Koutsky, L. Epidemiology of genital human papillomavirus infection. Am. J. Med., 1997, 102(5A), 3-8. doi: 10.1016/S0002-9343(97)00177-0 PMID: 9217656
- Chesson, H.W.; Dunne, E.F.; Hariri, S.; Markowitz, L.E. The estimated lifetime probability of acquiring human papillomavirus in the United States. Sex. Transm. Dis., 2014, 41(11), 660-664. doi: 10.1097/OLQ.0000000000000193 PMID: 25299412
- Koshiol, J.; Lindsay, L.; Pimenta, J.M.; Poole, C.; Jenkins, D.; Smith, J.S. Persistent human papillomavirus infection and cervical neoplasia: a systematic review and meta-analysis. Am. J. Epidemiol., 2008, 168(2), 123-137. doi: 10.1093/aje/kwn036 PMID: 18483125
- Schiffman, M. Integration of human papillomavirus vaccination, cytology, and human papillomavirus testing. Cancer, 2007, 111(3), 145-153. doi: 10.1002/cncr.22751 PMID: 17487850
- Gheit, T. Mucosal and cutaneous human papillomavirus infections and cancer biology. Front. Oncol., 2019, 9(355) doi: 10.3389/fonc.2019.00355 PMID: 31134154
- Bouvard, V.; Baan, R.; Straif, K.; Grosse, Y.; Secretan, B.; Ghissassi, F.E.; Benbrahim-Tallaa, L.; Guha, N.; Freeman, C.; Galichet, L.; Cogliano, V. A review of human carcinogensPart B: biological agents. Lancet Oncol., 2009, 10(4), 321-322. doi: 10.1016/S1470-2045(09)70096-8 PMID: 19350698
- Saraiya, M.; Unger, E.R.; Thompson, T.D.; Lynch, C.F.; Hernandez, B.Y.; Lyu, C.W.; Steinau, M.; Watson, M.; Wilkinson, E.J.; Hopenhayn, C.; Copeland, G.; Cozen, W.; Peters, E.S.; Huang, Y.; Saber, M.S.; Altekruse, S.; Goodman, M.T. US assessment of HPV types in cancers: implications for current and 9-valent HPV vaccines. J. Natl. Cancer Inst., 2015, 107(6), djv086. doi: 10.1093/jnci/djv086 PMID: 25925419
- Harper, D.M.; DeMars, L.R. HPV vaccines A review of the first decade. Gynecol. Oncol., 2017, 146(1), 196-204. doi: 10.1016/j.ygyno.2017.04.004 PMID: 28442134
- Stanley, M.A. Genital human papillomavirus infections: current and prospective therapies. J. Gen. Virol., 2012, 93(4), 681-691. doi: 10.1099/vir.0.039677-0 PMID: 22323530
- Stanley, M.A. Epithelial cell responses to infection with human papillomavirus. Clin. Microbiol. Rev., 2012, 25(2), 215-222. doi: 10.1128/CMR.05028-11 PMID: 22491770
- Graham, S.V. The human papillomavirus replication cycle, and its links to cancer progression: a comprehensive review. Clin. Sci. (Lond.), 2017, 131(17), 2201-2221. doi: 10.1042/CS20160786 PMID: 28798073
- Graham, S.V. Human papillomavirus: gene expression, regulation and prospects for novel diagnostic methods and antiviral therapies. Future Microbiol., 2010, 5(10), 1493-1506. doi: 10.2217/fmb.10.107 PMID: 21073310
- Bernard, H.U.; Burk, R.D.; Chen, Z.; van Doorslaer, K.; Hausen, H.; de Villiers, E.M. Classification of papillomaviruses (PVs) based on 189 PV types and proposal of taxonomic amendments. Virology, 2010, 401(1), 70-79. doi: 10.1016/j.virol.2010.02.002 PMID: 20206957
- Reference Clones, H.P.V. HPV reference clones. International Human Papillomavirus Reference Center. , 2022. Available from:https://www.hpvcenter.se/human_ reference_clones/
- Lowy, D.R.; Solomon, D.; Hildesheim, A.; Schiller, J.T.; Schiffman, M. Human papillomavirus infection and the primary and secondary prevention of cervical cancer. Cancer, 2008, 113(S7)(Suppl.), 1980-1993. doi: 10.1002/cncr.23704 PMID: 18798536
- Kavanagh, K.; Pollock, K.G.; Cuschieri, K.; Palmer, T.; Cameron, R.L.; Watt, C.; Bhatia, R.; Moore, C.; Cubie, H.; Cruickshank, M.; Robertson, C. Changes in the prevalence of human papillomavirus following a national bivalent human papillomavirus vaccination programme in Scotland: a 7-year cross-sectional study. Lancet Infect. Dis., 2017, 17(12), 1293-1302. doi: 10.1016/S1473-3099(17)30468-1 PMID: 28965955
- Arbyn, M.; Tommasino, M.; Depuydt, C.; Dillner, J. Are 20 human papillomavirus types causing cervical cancer? J. Pathol., 2014, 234(4), 431-435. doi: 10.1002/path.4424 PMID: 25124771
- Fradet-Turcotte, A.; Archambault, J. Recent advances in the search for antiviral agents against human papillomaviruses. Antivir. Ther., 2007, 12(4), 431-451. doi: 10.1177/135965350701200417 PMID: 17668552
- DAbramo, C.M.; Archambault, J. Small molecule inhibitors of human papillomavirus protein - protein interactions. Open Virol. J., 2011, 5(1), 80-95. doi: 10.2174/1874357901105010080 PMID: 21769307
- Messa, L.; Loregian, A. HPV-induced cancers: preclinical therapeutic advancements. Expert Opin. Investig. Drugs, 2022, 31(1), 79-93. doi: 10.1080/13543784.2021.2010703 PMID: 34927502
- Bergvall, M.; Melendy, T.; Archambault, J. The E1 proteins. Virology, 2013, 445(1-2), 35-56. doi: 10.1016/j.virol.2013.07.020 PMID: 24029589
- McBride, A.A. The papillomavirus E2 proteins. Virology, 2013, 445(1-2), 57-79. doi: 10.1016/j.virol.2013.06.006 PMID: 23849793
- White, P.W.; Faucher, A-M.; Goudreau, N. Small Molecule Inhibitors of the Human Papillomavirus E1-E2 Interaction. In: Small-Molecule Inhibitors of Protein-Protein Interactions; Vassilev, L.; Fry, D., Eds.; Springer Berlin Heidelberg: Berlin, Heidelberg, 2010; pp. 61-88. doi: 10.1007/82_2010_92
- Faucher, A.M.; White, P.W.; Brochu, C.; Grand-Maître, C.; Rancourt, J.; Fazal, G. Discovery of small-molecule inhibitors of the ATPase activity of human papillomavirus E1 helicase. J. Med. Chem., 2004, 47(1), 18-21. doi: 10.1021/jm034206x PMID: 14695816
- White, P.W.; Faucher, A.M.; Massariol, M.J.; Welchner, E.; Rancourt, J.; Cartier, M.; Archambault, J. Biphenylsulfonacetic acid inhibitors of the human papillomavirus type 6 E1 helicase inhibit ATP hydrolysis by an allosteric mechanism involving tyrosine 486. Antimicrob. Agents Chemother., 2005, 49(12), 4834-4842. doi: 10.1128/AAC.49.12.4834-4842.2005 PMID: 16304143
- Lu, X.; Zhang, Y.; Chen, S.; Li, Y.; Jia, D.; Wang, W.; Gao, B.; Liu, H. Molecular dynamics simulation study on the mechanism of the inhibition of ATP hydrolysis with inhibitors in human papillomavirus type 18 E1 helicase. 2013, 44-47. doi: 10.2991/iccnce.2013.12
- Iryani, I.; Amelia, F.; Iswendi, I. Active sites prediction and binding analysis E1-E2 protein human papillomavirus with biphenylsulfonacetic acid. IOP Conf. Series Mater. Sci. Eng., 2018, 335, 012031. doi: 10.1088/1757-899X/335/1/012031
- White, P.W.; Titolo, S.; Brault, K.; Thauvette, L.; Pelletier, A.; Welchner, E.; Bourgon, L.; Doyon, L.; Ogilvie, W.W.; Yoakim, C.; Cordingley, M.G.; Archambault, J. Inhibition of human papillomavirus DNA replication by small molecule antagonists of the E1-E2 protein interaction. J. Biol. Chem., 2003, 278(29), 26765-26772. doi: 10.1074/jbc.M303608200 PMID: 12730224
- Berg, M.; Stenlund, A. Functional interactions between papillomavirus E1 and E2 proteins. J. Virol., 1997, 71(5), 3853-3863. doi: 10.1128/jvi.71.5.3853-3863.1997 PMID: 9094661
- Yoakim, C.; Ogilvie, W.W.; Goudreau, N.; Naud, J.; Haché, B.; OMeara, J.A.; Cordingley, M.G.; Archambault, J.; White, P.W. Discovery of the first series of inhibitors of human papillomavirus type 11: inhibition of the assembly of the E1E2Origin DNA complex. Bioorg. Med. Chem. Lett., 2003, 13(15), 2539-2541. doi: 10.1016/S0960-894X(03)00510-9 PMID: 12852961
- Davidson, W.; McGibbon, G.A.; White, P.W.; Yoakim, C.; Hopkins, J.L.; Guse, I.; Hambly, D.M.; Frego, L.; Ogilvie, W.W.; Lavallée, P.; Archambault, J. Characterization of the binding site for inhibitors of the HPV11 E1-E2 protein interaction on the E2 transactivation domain by photoaffinity labeling and mass spectrometry. Anal. Chem., 2004, 76(7), 2095-2102. doi: 10.1021/ac035335o PMID: 15053675
- Goudreau, N.; Cameron, D.R.; Déziel, R.; Haché, B.; Jakalian, A.; Malenfant, E.; Naud, J.; Ogilvie, W.W.; OMeara, J.; White, P.W.; Yoakim, C. Optimization and determination of the absolute configuration of a series of potent inhibitors of human papillomavirus type-11 E1E2 proteinprotein interaction: A combined medicinal chemistry, NMR and computational chemistry approach. Bioorg. Med. Chem., 2007, 15(7), 2690-2700. doi: 10.1016/j.bmc.2007.01.036 PMID: 17306550
- Wang, Y.; Coulombe, R.; Cameron, D.R.; Thauvette, L.; Massariol, M.J.; Amon, L.M.; Fink, D.; Titolo, S.; Welchner, E.; Yoakim, C.; Archambault, J.; White, P.W. Crystal structure of the E2 transactivation domain of human papillomavirus type 11 bound to a protein interaction inhibitor. J. Biol. Chem., 2004, 279(8), 6976-6985. doi: 10.1074/jbc.M311376200 PMID: 14634007
- Moggio, Y.; Legnani, L.; Bovio, B.; Memeo, M.G.; Quadrelli, P. Synthesis of novel anthracene derivatives of isoxazolino-carbocyclic nucleoside analogues. Tetrahedron, 2012, 68(5), 1384-1392. doi: 10.1016/j.tet.2011.12.047
- Memeo, M.G.; Lapolla, F.; Maga, G.; Quadrelli, P. Synthesis and antiviral activity of anthracene derivatives of isoxazolino-carbocyclic nucleoside analogues. Tetrahedron Lett., 2015, 56(15), 1986-1990. doi: 10.1016/j.tetlet.2015.02.114
- Al-Saad, D.; Memeo, M.G.; Quadrelli, P. Pericyclic reactions for anti-HPV antivirals: Unconventional nucleoside analogue synthesis via nitrosocarbonyl chemistry. ChemistrySelect, 2017, 2(32), 10340-10346. doi: 10.1002/slct.201702059
- Dalya, A-S.; Misal, G.M.; Paolo, Q. Pericyclic reactions for antivirals: Synthesis of 4-bromo-N-(1R*,4S*)-4-hydroxy-2-cyclohexen-1-yl-2-thiazolecarboxamide. Lett. Org. Chem., 2016, 13(10), 757-763.
- Hajduk, P.J.; Dinges, J.; Miknis, G.F.; Merlock, M.; Middleton, T.; Kempf, D.J.; Egan, D.A.; Walter, K.A.; Robins, T.S.; Shuker, S.B.; Holzman, T.F.; Fesik, S.W. NMR-based discovery of lead inhibitors that block DNA binding of the human papillomavirus E2 protein. J. Med. Chem., 1997, 40(20), 3144-3150. doi: 10.1021/jm9703404 PMID: 9379433
- Yanofsky, V.R.; Patel, R.V.; Goldenberg, G. Genital warts: a comprehensive review. J. Clin. Aesthet. Dermatol., 2012, 5(6), 25-36. PMID: 22768354
- Saitoh, T.; Kuramochi, K.; Imai, T.; Takata, K.; Takehara, M.; Kobayashi, S.; Sakaguchi, K.; Sugawara, F. Podophyllotoxin directly binds a hinge domain in E2 of HPV and inhibits an E2/E7 interaction in vitro. Bioorg. Med. Chem., 2008, 16(10), 5815-5825. doi: 10.1016/j.bmc.2008.03.053 PMID: 18396405
- de Planell-Mas, E.; Martínez-Garriga, B.; Zalacain, A.J.; Vinuesa, T.; Viñas, M. Human papillomaviruses genotyping in plantar warts. J. Med. Virol., 2017, 89(5), 902-907. doi: 10.1002/jmv.24713 PMID: 27736001
- Gammoh, N.; Isaacson, E.; Tomaić, V.; Jackson, D.J.; Doorbar, J.; Banks, L. Inhibition of HPV-16 E7 oncogenic activity by HPV-16 E2. Oncogene, 2009, 28(23), 2299-2304. doi: 10.1038/onc.2009.78 PMID: 19421149
- Wang, X.; Helfer, C.M.; Pancholi, N.; Bradner, J.E.; You, J. Recruitment of Brd4 to the human papillomavirus type 16 DNA replication complex is essential for replication of viral DNA. J. Virol., 2013, 87(7), 3871-3884. doi: 10.1128/JVI.03068-12 PMID: 23365439
- Helfer, C.M.; Wang, R.; You, J. Analysis of the papillomavirus E2 and bromodomain protein Brd4 interaction using bimolecular fluorescence complementation. PLoS One, 2013, 8(10), e77994. doi: 10.1371/journal.pone.0077994 PMID: 24205059
- Helfer, C.; Yan, J.; You, J. The cellular bromodomain protein Brd4 has multiple functions in E2-mediated papillomavirus transcription activation. Viruses, 2014, 6(8), 3228-3249. doi: 10.3390/v6083228 PMID: 25140737
- Morse, M.A.; Balogh, K.K.; Brendle, S.A.; Campbell, C.A.; Chen, M.X.; Furze, R.C.; Harada, I.L.; Holyer, I.D.; Kumar, U.; Lee, K.; Prinjha, R.K.; Rüdiger, M.; Seal, J.T.; Taylor, S.; Witherington, J.; Christensen, N.D. BET bromodomain inhibitors show anti-papillomavirus activity in vitro and block CRPV wart growth in vivo. Antiviral Res., 2018, 154, 158-165. doi: 10.1016/j.antiviral.2018.03.012 PMID: 29653131
- Doorbar, J. The E4 protein; structure, function and patterns of expression. Virology, 2013, 445(1-2), 80-98. doi: 10.1016/j.virol.2013.07.008 PMID: 24016539
- Davy, C.E.; Jackson, D.J.; Wang, Q.; Raj, K.; Masterson, P.J.; Fenner, N.F.; Southern, S.; Cuthill, S.; Millar, J.B.A.; Doorbar, J. Identification of a G(2) arrest domain in the E1 wedge E4 protein of human papillomavirus type 16. J. Virol., 2002, 76(19), 9806-9818. doi: 10.1128/JVI.76.19.9806-9818.2002 PMID: 12208959
- Piirsoo, A.; Piirsoo, M.; Kala, M.; Sankovski, E.; Lototskaja, E.; Levin, V.; Salvi, M.; Ustav, M. Activity of CK2α protein kinase is required for efficient replication of some HPV types. PLoS Pathog., 2019, 15(5), e1007788. doi: 10.1371/journal.ppat.1007788 PMID: 31091289
- Wolfgang, G.H.I.; Shibata, R.; Wang, J.; Ray, A.S.; Wu, S.; Doerrfler, E.; Reiser, H.; Lee, W.A.; Birkus, G.; Christensen, N.D.; Andrei, G.; Snoeck, R. GS-9191 is a novel topical prodrug of the nucleotide analog 9-(2-phosphonylmethoxyethyl)guanine with antiproliferative activity and possible utility in the treatment of human papillomavirus lesions. Antimicrob. Agents Chemother., 2009, 53(7), 2777-2784. doi: 10.1128/AAC.00103-09 PMID: 19398642
- Safety and Effectiveness Study of an Experimental Topical Ointment (GS-9191) for the Treatment of Genital Warts. NCT00499967, 2009.
- Valiaeva, N.; Trahan, J.; Aldern, K.A.; Beadle, J.R.; Hostetler, K.Y. Antiproliferative effects of octadecyloxyethyl 9-2-(phosphonomethoxy)ethylguanine against Me-180 human cervical cancer cells in vitro and in vivo. Chemotherapy, 2010, 56(1), 54-59. doi: 10.1159/000292582 PMID: 20215748
- Beadle, J.R.; Valiaeva, N.; Yang, G.; Yu, J.H.; Broker, T.R.; Aldern, K.A.; Harden, E.A.; Keith, K.A.; Prichard, M.N.; Hartman, T.; Buckheit, R.W., Jr; Chow, L.T.; Hostetler, K.Y. Synthesis and antiviral evaluation of octadecyloxyethyl benzyl 9-(2-phosphonomethoxy)ethyl guanine (ODE-Bn-PMEG), a potent inhibitor of transient HPV DNA amplification. J. Med. Chem., 2016, 59(23), 10470-10478. doi: 10.1021/acs.jmedchem.6b00659 PMID: 27933957
- Banerjee, N.S.; Wang, H.K.; Beadle, J.R.; Hostetler, K.Y.; Chow, L.T. Evaluation of ODE-Bn-PMEG, an acyclic nucleoside phosphonate prodrug, as an antiviral against productive HPV infection in 3D organotypic epithelial cultures. Antiviral Res., 2018, 150, 164-173. doi: 10.1016/j.antiviral.2017.12.013 PMID: 29287913
- Study of Topical ABI-1968 in Subjects with Precancerous Anal Lesions Resulting from Human Papillomavirus (HPV) Infection NCT03202992 2017.
- Study of Topical ABI-1968 in Subjects with Precancerous Cervical Lesions from Human Papillomavirus (HPV) Infection. NCT03697226, 2018.
- Study of Topical ABI-1968 in Subjects with Precancerous Cervical Lesions from Human Papillomavirus (HPV) Infection NCT03239223 2017.
- Study of Topical ABI-1968 in Subjects with Precancerous Anal Lesions Resulting from Human Papillomavirus (HPV) Infection NCT03677960 2018.
- Toots, M.; Ustav, M., Jr; Männik, A.; Mumm, K.; Tämm, K.; Tamm, T.; Ustav, E.; Ustav, M. Identification of several high-risk HPV inhibitors and drug targets with a novel high-throughput screening assay. PLoS Pathog., 2017, 13(2), e1006168. doi: 10.1371/journal.ppat.1006168 PMID: 28182794
- Estêvão, D.; Costa, N.R.; Gil da Costa, R.M.; Medeiros, R. Hallmarks of HPV carcinogenesis: The role of E6, E7 and E5 oncoproteins in cellular malignancy. Gene Regulatory Mechanisms., 2019, 1862(2), 153-162. PMID: 30707946
- Buitrago-Pérez, A.; Garaulet, G.; Vázquez-Carballo, A.; Paramio, J.; García-Escudero, R. Molecular signature of HPV-induced carcinogenesis: pRb, p53 and gene expression profiling. Curr. Genomics, 2009, 10(1), 26-34. doi: 10.2174/138920209787581235 PMID: 19721808
- Giacinti, C.; Giordano, A. RB and cell cycle progression. Oncogene, 2006, 25(38), 5220-5227. doi: 10.1038/sj.onc.1209615 PMID: 16936740
- Tommasino, M.; Crawford, L. Human papillomavirus E6 and E7: Proteins which deregulate the cell cycle. BioEssays, 1995, 17(6), 509-518. doi: 10.1002/bies.950170607 PMID: 7575492
- Sak, K. Characteristic features of cytotoxic activity of flavonoids on human cervical cancer cells. Asian Pac. J. Cancer Prev., 2014, 15(19), 8007-8018. doi: 10.7314/APJCP.2014.15.19.8007 PMID: 25338977
- Moga, M.; Dimienescu, O.; Arvatescu, C.; Mironescu, A.; Dracea, L.; Ples, L. The role of natural polyphenols in the prevention and treatment of cervical cancerAn overview. Molecules, 2016, 21(8), 1055. doi: 10.3390/molecules21081055 PMID: 27548122
- Yuan, C.H.; Filippova, M.; Tungteakkhun, S.S.; Duerksen-Hughes, P.J.; Krstenansky, J.L. Small molecule inhibitors of the HPV16-E6 interaction with caspase 8. Bioorg. Med. Chem. Lett., 2012, 22(5), 2125-2129. doi: 10.1016/j.bmcl.2011.12.145 PMID: 22300659
- Cherry, J.J.; Rietz, A.; Malinkevich, A.; Liu, Y.; Xie, M.; Bartolowits, M.; Davisson, V.J.; Baleja, J.D.; Androphy, E.J. Structure based identification and characterization of flavonoids that disrupt human papillomavirus-16 E6 function. PLoS One, 2013, 8(12), e84506. doi: 10.1371/journal.pone.0084506 PMID: 24376816
- Huibregtse, J.M.; Scheffner, M.; Howley, P.M. A cellular protein mediates association of p53 with the E6 oncoprotein of human papillomavirus types 16 or 18. EMBO J., 1991, 10(13), 4129-4135. doi: 10.1002/j.1460-2075.1991.tb04990.x PMID: 1661671
- Rietz, A.; Petrov, D.P.; Bartolowits, M.; DeSmet, M.; Davisson, V.J.; Androphy, E.J. Molecular probing of the HPV-16 E6 protein alpha helix binding groove with small molecule inhibitors. PLoS One, 2016, 11(2), e0149845. doi: 10.1371/journal.pone.0149845 PMID: 26915086
- Clemente-Soto, A.F.; Salas-Vidal, E.; Milan-Pacheco, C.; Sánchez-Carranza, J.N.; Peralta-Zaragoza, O.; González-Maya, L. Quercetin induces G2 phase arrest and apoptosis with the activation of p53 in an E6 expression independent manner in HPV positive human cervical cancer derived cells. Mol. Med. Rep., 2019, 19(3), 2097-2106. doi: 10.3892/mmr.2019.9850 PMID: 30664221
- Yuan, C-H.; Filippova, M.; Krstenansky, J.L.; Duerksen-Hughes, P.J. Flavonol and imidazole derivatives block HPV16 E6 activities and reactivate apoptotic pathways in HPV+ cells. Cell Death Dis., 2016, 7(1), e2060. doi: 10.1038/cddis.2015.391 PMID: 26794656
- Malecka, K.A.; Fera, D.; Schultz, D.C.; Hodawadekar, S.; Reichman, M.; Donover, P.S.; Murphy, M.E.; Marmorstein, R. Identification and characterization of small molecule human papillomavirus E6 inhibitors. ACS Chem. Biol., 2014, 9(7), 1603-1612. doi: 10.1021/cb500229d PMID: 24854633
- Bisol, .; Campos, P.S.; Lamers, M.L. Flavonoids as anticancer therapies: A systematic review of clinical trials. Phytother. Res., 2020, 34(3), 568-582. doi: 10.1002/ptr.6551 PMID: 31752046
- Ahn, W-S.; Yoo, J.; Huh, S-W.; Kim, C-K.; Lee, J-M.; Namkoong, S-E.; Bae, S-M.; Lee, I.P. Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions. Eur. J. Cancer Prev., 2003, 12(5), 383-390. doi: 10.1097/00008469-200310000-00007 PMID: 14512803
- Ahn, W.S.; Huh, S.W.; Bae, S.M.; Lee, I.P.; Lee, J.M.; Namkoong, S.E.; Kim, C.K.; Sin, J.I. A major constituent of green tea, EGCG, inhibits the growth of a human cervical cancer cell line, CaSki cells, through apoptosis, G(1) arrest, and regulation of gene expression. DNA Cell Biol., 2003, 22(3), 217-224. doi: 10.1089/104454903321655846 PMID: 12804120
- Qiao, Y.; Cao, J.; Xie, L.; Shi, X. Cell growth inhibition and gene expression regulation by (-)-epigallocatechin-3-gallate in human cervical cancer cells. Arch. Pharm. Res., 2009, 32(9), 1309-1315. doi: 10.1007/s12272-009-1917-3 PMID: 19784588
- Wang, Y.Q.; Lu, J.L.; Liang, Y.R.; Li, Q.S. Suppressive effects of EGCG on cervical cancer. Molecules, 2018, 23(9), 2334. doi: 10.3390/molecules23092334 PMID: 30213130
- He, L.; Zhang, E.; Shi, J.; Li, X.; Zhou, K.; Zhang, Q.; Le, A.D.; Tang, X. (−)-Epigallocatechin-3-gallate inhibits human papillomavirus (HPV)-16 oncoprotein-induced angiogenesis in non-small cell lung cancer cells by targeting HIF-1α. Cancer Chemother. Pharmacol., 2013, 71(3), 713-725. doi: 10.1007/s00280-012-2063-z PMID: 23292117
- Jun, J.C.; Rathore, A.; Younas, H.; Gilkes, D.; Polotsky, V.Y. Hypoxia-inducible factors and cancer. Curr. Sleep Med. Rep., 2017, 3(1), 1-10. doi: 10.1007/s40675-017-0062-7 PMID: 28944164
- Tang, X.; Zhang, Q.; Nishitani, J.; Brown, J.; Shi, S.; Le, A.D. Overexpression of human papillomavirus type 16 oncoproteins enhances hypoxia-inducible factor 1 α protein accumulation and vascular endothelial growth factor expression in human cervical carcinoma cells. Clin. Cancer Res., 2007, 13(9), 2568-2576. doi: 10.1158/1078-0432.CCR-06-2704 PMID: 17473185
- Natarajan, T.; Anandhi, M.; Aiswarya, D.; Ramkumar, R.; Kumar, S.; Perumal, P. Idaein chloride induced p53 dependent apoptosis in cervical cancer cells through inhibition of viral oncoproteins. Biochimie, 2016, 121, 13-20. doi: 10.1016/j.biochi.2015.11.008 PMID: 26586108
- Elbendary, A.A.; Cirisano, F.D.; Evans, A.C., Jr; Davis, P.L.; Iglehart, J.D.; Marks, J.R.; Berchuck, A. Relationship between p21 expression and mutation of the p53 tumor suppressor gene in normal and malignant ovarian epithelial cells. Clin. Cancer Res., 1996, 2(9), 1571-1575. PMID: 9816335
- Chatterjee, K.; AlSharif, D.; Mazza, C.; Syar, P.; Al Sharif, M.; Fata, J. Resveratrol and pterostilbene exhibit anticancer properties involving the downregulation of HPV oncoprotein E6 in cervical cancer cells. Nutrients, 2018, 10(2), 243. doi: 10.3390/nu10020243 PMID: 29485619
- Chatterjee, K.; Mukherjee, S.; Vanmanen, J.; Banerjee, P.; Fata, J.E. Dietary polyphenols, resveratrol and pterostilbene exhibit antitumor activity on an HPV E6-positive cervical cancer model: An in vitro and in vivo analysis. Front. Oncol., 2019, 9, 352. doi: 10.3389/fonc.2019.00352 PMID: 31143704
- Sun, X.; Fu, P.; Xie, L.; Chai, S.; Xu, Q.; Zeng, L.; Wang, X.; Jiang, N.; Sang, M. Resveratrol inhibits the progression of cervical cancer by suppressing the transcription and expression of HPV E6 and E7 genes. Int. J. Mol. Med., 2020, 47(1), 335-345. doi: 10.3892/ijmm.2020.4789 PMID: 33236130
- Flowers, L. Topical Curcumin for Precancer Cervical Lesions. NCT02944578, 2016. https://clinicaltrials.gov/ct2/show/NCT02944578
- Flowers, L. Topical Curcumin for HPV Related Cervical Disease. NCT04266275, 2020. https://clinicaltrials.gov/ct2/show/NCT04266275
- Teymouri, M.; Pirro, M.; Johnston, T.P.; Sahebkar, A. Curcumin as a multifaceted compound against human papilloma virus infection and cervical cancers: A review of chemistry, cellular, molecular, and preclinical features. Biofactors, 2017, 43(3), 331-346. doi: 10.1002/biof.1344 PMID: 27896883
- Divya, C.S.; Pillai, M.R. Antitumor action of curcumin in human papillomavirus associated cells involves downregulation of viral oncogenes, prevention of NFkB and AP-1 translocation, and modulation of apoptosis. Mol. Carcinog., 2006, 45(5), 320-332. doi: 10.1002/mc.20170 PMID: 16526022
- Nelson, K.M.; Dahlin, J.L.; Bisson, J.; Graham, J.; Pauli, G.F.; Walters, M.A. The essential medicinal chemistry of curcumin. J. Med. Chem., 2017, 60(5), 1620-1637. doi: 10.1021/acs.jmedchem.6b00975 PMID: 28074653
- Rastogi, N.; Duggal, S.; Singh, S.K.; Porwal, K.; Srivastava, V.K.; Maurya, R.; Bhatt, M.L.B.; Mishra, D.P. Proteasome inhibition mediates p53 reactivation and anti-cancer activity of 6-Gingerol in cervical cancer cells. Oncotarget, 2015, 6(41), 43310-43325. doi: 10.18632/oncotarget.6383 PMID: 26621832
- Zivarpour, P.; Nikkhah, E.; Maleki Dana, P.; Asemi, Z.; Hallajzadeh, J. Molecular and biological functions of gingerol as a natural effective therapeutic drug for cervical cancer. J. Ovarian Res., 2021, 14(1), 43. doi: 10.1186/s13048-021-00789-x PMID: 33706784
- Kashyap, V.K.; Dan, N.; Chauhan, N.; Wang, Q.; Setua, S.; Nagesh, P.K.B.; Malik, S.; Batra, V.; Yallapu, M.M.; Miller, D.D.; Li, W.; Hafeez, B.B.; Jaggi, M.; Chauhan, S.C. VERU-111 suppresses tumor growth and metastatic phenotypes of cervical cancer cells through the activation of p53 signaling pathway. Cancer Lett., 2020, 470, 64-74. doi: 10.1016/j.canlet.2019.11.035 PMID: 31809801
- Hassan, A.Y.; El-Sebaey, S.A.; El Deeb, M.A.; Elzoghbi, M.S. Potential antiviral and anticancer effect of imidazoles and bridgehead imidazoles generated by HPV-Induced cervical carcinomas via reactivating the P53/pRb pathway and inhibition of CA IX. J. Mol. Struct., 2021, 1230, 129865. doi: 10.1016/j.molstruc.2020.129865
- Delgado, G.; Sulbaran, M.E.; Mora, A.J. Synthesis, crystal structure and hydrogen-bonding patterns in rac-N-acetyl-2-thiohydantoin-leucine. Int. J. Mat. Chem., 2013, 3(1), 1-4.
- Yim, E.K.; Lee, M.J.; Lee, K.H.; Um, S.J.; Park, J.S. Antiproliferative and antiviral mechanisms of ursolic acid and dexamethasone in cervical carcinoma cell lines. Int. J. Gynecol. Cancer, 2006, 16(6), 2023-2031. doi: 10.1111/j.1525-1438.2006.00726.x PMID: 17177841
- Paul, P.; Rajendran, S.K.; Peuhu, E.; Alshatwi, A.A.; Akbarsha, M.A.; Hietanen, S.; Eriksson, J.E. Novel action modality of the diterpenoid anisomelic acid causes depletion of E6 and E7 viral oncoproteins in HPV-transformed cervical carcinoma cells. Biochem. Pharmacol., 2014, 89(2), 171-184. doi: 10.1016/j.bcp.2014.02.011 PMID: 24565908
- Kuida, K. Caspase-9. Int. J. Biochem. Cell Biol., 2000, 32(2), 121-124. doi: 10.1016/S1357-2725(99)00024-2 PMID: 10687948
- Senthilkumar, R.; Brusentsev, Y.; Paul, P.; Marimuthu, P.; Cheng, F.; Eklund, P.C.; Eriksson, J.E. Synthesis and evaluation of anisomelic acid-like compounds for the treatment of HPV-mediated carcinomas. Sci. Rep., 2019, 9(1), 20295. doi: 10.1038/s41598-019-56410-1 PMID: 31889069
- Rocha, S.M.M.; Cardoso, P.C.S.; Bahia, M.O.; Pessoa, C.Ó.; Soares, P.C.; Rocha, S.M.; Burbano, R.M.R.; Rocha, C.A.M. Effect of the kaurenoic acid on genotoxicity and cell cycle progression in cervical cancer cells lines. Toxicol. In Vitro, 2019, 57, 126-131. doi: 10.1016/j.tiv.2019.02.022 PMID: 30822460
- Chitsike, L.; Yuan, C.H.; Roy, A.; Boyle, K.; Duerksen-Hughes, P.J. A high-content AlphaScreen identifies E6-specific small molecule inhibitors as potential therapeutics for HPV+ head and neck squamous cell carcinomas. Oncotarget, 2021, 12(6), 549-561. doi: 10.18632/oncotarget.27908 PMID: 33796223
- Han, Q.B.; Yang, L.; Wang, Y.L.; Qiao, C.F.; Song, J.Z.; Sun, H.D.; Xu, H.X. A pair of novel cytotoxic polyprenylated xanthone epimers from gamboges. Chem. Biodivers., 2006, 3(1), 101-105. doi: 10.1002/cbdv.200690000 PMID: 17193222
- Munagala, R.; Kausar, H.; Munjal, C.; Gupta, R.C. Withaferin A induces p53-dependent apoptosis by repression of HPV oncogenes and upregulation of tumor suppressor proteins in human cervical cancer cells. Carcinogenesis, 2011, 32(11), 1697-1705. doi: 10.1093/carcin/bgr192 PMID: 21859835
- Caicedo-Granados, E.; Lin, R.; Fujisawa, C.; Yueh, B.; Sangwan, V.; Saluja, A. Wild-type p53 reactivation by small-molecule Minnelide in human papillomavirus (HPV)-positive head and neck squamous cell carcinoma. Oral Oncol., 2014, 50(12), 1149-1156. doi: 10.1016/j.oraloncology.2014.09.013 PMID: 25311433
- Fang, Zy.; Zhang, M. Liu J-n, Zhao X, Zhang Y-q, Fang L. Tanshinone IIA: A review of its anticancer effects. Front. Pharmacol., 2021, 11(2189)
- Munagala, R.; Aqil, F.; Jeyabalan, J.; Gupta, R.C. Tanshinone IIA inhibits viral oncogene expression leading to apoptosis and inhibition of cervical cancer. Cancer Lett., 2015, 356(2)(2, Part B), 536-546. doi: 10.1016/j.canlet.2014.09.037 PMID: 25304375
- Li, M.; Wang, G.; Zhang, R.; Duan, S.; Chen, J. Tanshinone IIA inhibits proliferation and activates apoptosis in C4-1 cervical carcinoma cells in vitro. Biotechnol. Biotechnol. Equip., 2019, 33(1), 1599-1607. doi: 10.1080/13102818.2019.1677175
- Mahata, S.; Bharti, A.C.; Shukla, S.; Tyagi, A.; Husain, S.A.; Das, B.C. Berberine modulates AP-1 activity to suppress HPV transcription and downstream signaling to induce growth arrest and apoptosis in cervical cancer cells. Mol. Cancer, 2011, 10(1), 39. doi: 10.1186/1476-4598-10-39 PMID: 21496227
- Shaulian, E.; Karin, M. AP-1 in cell proliferation and survival. Oncogene, 2001, 20(19), 2390-2400. doi: 10.1038/sj.onc.1204383 PMID: 11402335
- Saha, S.K.; Khuda-Bukhsh, A.R. Berberine alters epigenetic modifications, disrupts microtubule network, and modulates HPV-18 E6E7 oncoproteins by targeting p53 in cervical cancer cell HeLa: A mechanistic study including molecular docking. Eur. J. Pharmacol., 2014, 744, 132-146. doi: 10.1016/j.ejphar.2014.09.048 PMID: 25448308
- Wang, Y.; Li, X.; Song, S.; Wu, J. Development of basal-like HaCaT keratinocytes containing the genome of human papillomavirus (HPV) type 11 for screening of anti-HPV effects. SLAS Discov., 2014, 19(8), 1154-1163. doi: 10.1177/1087057114536987 PMID: 24874507
- Mortazavi, H.; Nikfar, B.; Esmaeili, S.A.; Rafieenia, F.; Saburi, E.; Chaichian, S.; Heidari Gorji, M.A.; Momtazi-Borojeni, A.A. Potential cytotoxic and anti-metastatic effects of berberine on gynaecological cancers with drug-associated resistance. Eur. J. Med. Chem., 2020, 187, 111951. doi: 10.1016/j.ejmech.2019.111951 PMID: 31821990
- Dasari, S.; Bakthavachalam, V.; Chinnapaka, S.; Venkatesan, R.; Samy, A.L.P.A.; Munirathinam, G. Neferine, an alkaloid from lotus seed embryo targets HELA and SIHA cervical cancer cells via pro‐oxidant anticancer mechanism. Phytother. Res., 2020, 34(9), 2366-2384. doi: 10.1002/ptr.6687 PMID: 32364634
- Beerheide, W.; Bernard, H.U.; Tan, Y.J.; Ganesan, A.; Rice, W.G.; Ting, A.E. Potential drugs against cervical cancer: zinc-ejecting inhibitors of the human papillomavirus type 16 E6 oncoprotein. J. Natl. Cancer Inst., 1999, 91(14), 1211-1220. doi: 10.1093/jnci/91.14.1211 PMID: 10413422
- Beerheide, W.; Sim, M.M.; Tan, Y.J.; Bernard, H.U.; Ting, A.E. Inactivation of the human papillomavirus-16 e6 oncoprotein by organic disulfides. Bioorg. Med. Chem., 2000, 8(11), 2549-2560. doi: 10.1016/S0968-0896(00)00193-0 PMID: 11092540
- Fera, D.; Schultz, D.C.; Hodawadekar, S.; Reichman, M.; Donover, P.S.; Melvin, J.; Troutman, S.; Kissil, J.L.; Huryn, D.M.; Marmorstein, R. Identification and characterization of small molecule antagonists of pRb inactivation by viral oncoproteins. Chem. Biol., 2012, 19(4), 518-528. doi: 10.1016/j.chembiol.2012.03.007 PMID: 22520758
- Zhao, C.Y.; Szekely, L.; Bao, W.; Selivanova, G. Rescue of p53 function by small-molecule RITA in cervical carcinoma by blocking E6-mediated degradation. Cancer Res., 2010, 70(8), 3372-3381. doi: 10.1158/0008-5472.CAN-09-2787 PMID: 20395210
- Singh, M.; Modi, A.; Narayan, G.; Singh, S.K. Benzothiazole derivatives bearing amide moiety. Anticancer Drugs, 2016, 27(6), 519-532. doi: 10.1097/CAD.0000000000000357 PMID: 26945135
- Modi, A.; Singh, M.; Gutti, G.; Shanker, O.R.; Singh, V.K.; Singh, S.; Singh, S.K.; Pradhan, S.; Narayan, G. Benzothiazole derivative bearing amide moiety induces p53-mediated apoptosis in HPV16 positive cervical cancer cells. Invest. New Drugs, 2020, 38(4), 934-945. doi: 10.1007/s10637-019-00848-7 PMID: 31432292
- Celegato, M.; Messa, L.; Goracci, L.; Mercorelli, B.; Bertagnin, C.; Spyrakis, F.; Suarez, I.; Cousido-Siah, A.; Travé, G.; Banks, L.; Cruciani, G.; Palù, G.; Loregian, A. A novel small-molecule inhibitor of the human papillomavirus E6-p53 interaction that reactivates p53 function and blocks cancer cells growth. Cancer Lett., 2020, 470, 115-125. doi: 10.1016/j.canlet.2019.10.046 PMID: 31693922
- Hietanen, S.; Lain, S.; Krausz, E.; Blattner, C.; Lane, D.P. Activation of p53 in cervical carcinoma cells by small molecules. Proc. Natl. Acad. Sci. USA, 2000, 97(15), 8501-8506. doi: 10.1073/pnas.97.15.8501 PMID: 10900010
- Zhang, W.; Che, Q.; Tan, H.; Qi, X.; Li, J.; Li, D.; Gu, Q.; Zhu, T.; Liu, M. Marine Streptomyces sp. derived antimycin analogues suppress HeLa cells via depletion HPV E6/E7 mediated by ROS-dependent ubiquitinproteasome system. Sci. Rep., 2017, 7(1), 42180. doi: 10.1038/srep42180 PMID: 28176847
- Omura, S.; Iwai, Y.; Hirano, A.; Nakagawa, A.; Awaya, J.; Tsuchiya, H.; Takahashi, Y.; Asuma, R. A new alkaloid AM-2282 of Streptomyces origin taxonomy, fermentation, isolation and preliminary characterization. J. Antibiot. (Tokyo), 1977, 30(4), 275-282. doi: 10.7164/antibiotics.30.275 PMID: 863788
- Funato, N.; Takayanagi, H.; Konda, Y.; Toda, Y.; Harigaya, Y.; Iwai, Y.; Ōmura, S. Absolute configuration of staurosporine by X-Ray analysis. Tetrahedron Lett., 1994, 35(8), 1251-1254. doi: 10.1016/0040-4039(94)88036-0
- Bernard, B.; Fest, T.; Prétet, J-L.; Mougin, C. Staurosporine-induced apoptosis of HPV positive and negative human cervical cancer cells from different points in the cell cycle. Cell Death Differ., 2001, 8(3), 234-244. doi: 10.1038/sj.cdd.4400796 PMID: 11319606
- Bernard, B.; Prétet, J.L.; Charlot, J.F.; Mougin, C. Human papillomaviruses type 16+ and 18+ cervical carcinoma cells are sensitive to staurosporine-mediated apoptosis. Biol. Cell, 2003, 95(1), 17-26. doi: 10.1016/S0248-4900(02)01220-0 PMID: 12753950
- Decrion-Barthod, A-Z.; Bosset, M.; Plissonnier, M-L.; Marchini, A.; Nicolier, M.; Launay, S.; Prétet, J.L.; Rommelaere, J.; Mougin, C. Sodium butyrate with UCN-01 has marked antitumour activity against cervical cancer cells. Anticancer Res., 2010, 30(10), 4049-4061. PMID: 21036719
- Singh, S.B.; Zink, D.L.; Polishook, J.D.; Dombrowski, A.W.; Darkin-Rattray, S.J.; Schmatz, D.M.; Goetz, M.A. Apicidins: Novel cyclic tetrapeptides as coccidiostats and antimalarial agents from Fusarium pallidoroseum. Tetrahedron Lett., 1996, 37(45), 8077-8080. doi: 10.1016/0040-4039(96)01844-8
- Łuczak, M.W.; Jagodzinski, P.P. Apicidin down-regulates human papillomavirus type 16 E6 and E7 transcripts and proteins in SiHa cervical cancer cells. Cancer Lett., 2008, 272(1), 53-60. doi: 10.1016/j.canlet.2008.06.030 PMID: 18687520
- Baleja, J.D.; Cherry, J.J.; Liu, Z.; Gao, H.; Nicklaus, M.C.; Voigt, J.H.; Chen, J.J.; Androphy, E.J. Identification of inhibitors to papillomavirus type 16 E6 protein based on three-dimensional structures of interacting proteins. Antiviral Res., 2006, 72(1), 49-59. doi: 10.1016/j.antiviral.2006.03.014 PMID: 16690141
- Baylin, S.B. DNA methylation and gene silencing in cancer. Nat. Clin. Pract. Oncol., 2005, 2(S1)(Suppl. 1), S4-S11. doi: 10.1038/ncponc0354 PMID: 16341240
- Kalantari, M.; Lee, D.; Calleja-Macias, I.E.; Lambert, P.F.; Bernard, H.U. Effects of cellular differentiation, chromosomal integration and 5-aza-2′-deoxycytidine treatment on human papillomavirus-16 DNA methylation in cultured cell lines. Virology, 2008, 374(2), 292-303. doi: 10.1016/j.virol.2007.12.016 PMID: 18242658
- Zhang, C.; Deng, Z.; Pan, X.; Uehara, T.; Suzuki, M.; Xie, M. Effects of methylation status of CpG sites within the HPV16 long control region on HPV16-positive head and neck cancer cells. PLoS One, 2015, 10(10), e0141245. doi: 10.1371/journal.pone.0141245 PMID: 26509736
- Stich, M.; Ganss, L.; Puschhof, J.; Prigge, E.S.; Reuschenbach, M.; Guiterrez, A.; Vinokurova, S.; von Knebel Doeberitz, M. 5-aza-2′-deoxycytidine (DAC) treatment downregulates the HPV E6 and E7 oncogene expression and blocks neoplastic growth of HPV-associated cancer cells. Oncotarget, 2017, 8(32), 52104-52117. doi: 10.18632/oncotarget.10631 PMID: 28881717
- Jung, H.M.; Phillips, B.L.; Chan, E.K.L. miR-375 activates p21 and suppresses telomerase activity by coordinately regulating HPV E6/E7, E6AP, CIP2A, and 14-3-3ζ. Mol. Cancer, 2014, 13(1), 80. doi: 10.1186/1476-4598-13-80 PMID: 24708873
- Morel, A.; Baguet, A.; Perrard, J.; Demeret, C.; Jacquin, E.; Guenat, D.; Mougin, C.; Prétet, J.L. 5azadC treatment upregulates miR-375 level and represses HPV16 E6 expression. Oncotarget, 2017, 8(28), 46163-46176. doi: 10.18632/oncotarget.17575 PMID: 28521287
- Perrard, J.; Morel, A.; Meznad, K.; Paget-Bailly, P.; Dalstein, V.; Guenat, D.; Mourareau, C.; Clavel, C.; Fauconnet, S.; Baguet, A.; Mougin, C.; Pretet, J.L. DNA demethylation agent 5azadC downregulates HPV16 E6 expression in cervical cancer cell lines independently of TBX2 expression. Oncol. Lett., 2020, 19(1), 1074-1081. PMID: 31897221
- Debus, J. Decitabine Treatment in HPV-Induced Anogenital and Head and Neck Cancer Patients after Radiotherapy or as Novel Late Salvage (DERANO). NCT04252248, 2020.
- Burtness, B. 5-Azacytidine and/or Nivolumab in Resectable HPV-Associated HNSCC. NCT05317000, 2022.
- He, H.; Liu, X.; Wang, D.; Wang, Y.; Liu, L.; Zhou, H.; Luo, X.; Wang, N.; Ji, B.; Luo, Y.; Zhang, T. SAHA inhibits the transcription initiation of HPV18 E6/E7 genes in HeLa cervical cancer cells. Gene, 2014, 553(2), 98-104. doi: 10.1016/j.gene.2014.10.007 PMID: 25300249
- Finzer, P.; Krueger, A.; Stöhr, M.; Brenner, D.; Soto, U.; Kuntzen, C.; Krammer, P.H.; Rösl, F. HDAC inhibitors trigger apoptosis in HPV-positive cells by inducing the E2Fp73 pathway. Oncogene, 2004, 23(28), 4807-4817. doi: 10.1038/sj.onc.1207620 PMID: 15077164
- Messa, L.; Celegato, M.; Bertagnin, C.; Mercorelli, B.; Nannetti, G.; Palù, G.; Loregian, A. A quantitative LumiFluo assay to test inhibitory compounds blocking p53 degradation induced by human papillomavirus oncoprotein E6 in living cells. Sci. Rep., 2018, 8(1), 6020. doi: 10.1038/s41598-018-24470-4 PMID: 29662081
- Sheaffer, A.K.; Lee, M.S.; Qi, H.; Chaniewski, S.; Zheng, X.; Farr, G.A. A small molecule inhibitor selectively induces apoptosis in cells transformed by high risk human papilloma viruses. PloS one, 2016, 11(6), e0155909. doi: 10.1371/journal.pone.0155909
- Han, F.; Li, Y.; Lu, Q.; Ma, L.; Wang, H.; Jiang, J.; Li, Z.; Li, Y. 3-(2-Chloropropyl amide)-4-methoxy-N-phenylbenzamide inhibits expression of HPV oncogenes in human cervical cancer cell. Virol. J., 2017, 14(1), 145. doi: 10.1186/s12985-017-0806-5 PMID: 28754129
- Willems, E.; Dedobbeleer, M.; Digregorio, M.; Lombard, A.; Lumapat, P.N.; Rogister, B. The functional diversity of Aurora kinases: a comprehensive review. Cell Div., 2018, 13(1), 7. doi: 10.1186/s13008-018-0040-6 PMID: 30250494
- Vader, G.; Lens, S.M.A. The Aurora kinase family in cell division and cancer. Biochimica et Biophysica Acta (BBA). Rev. Can., 2008, 1786(1), 60-72.
- Gabrielli, B.; Bokhari, F.; Ranall, M.V.; Oo, Z.Y.; Stevenson, A.J.; Wang, W.; Murrell, M.; Shaikh, M.; Fallaha, S.; Clarke, D.; Kelly, M.; Sedelies, K.; Christensen, M.; McKee, S.; Leggatt, G.; Leo, P.; Skalamera, D.; Soyer, H.P.; Gonda, T.J.; McMillan, N.A.J. Aurora A is critical for survival in HPV-transformed cervical cancer. Mol. Cancer Ther., 2015, 14(12), 2753-2761. doi: 10.1158/1535-7163.MCT-15-0506 PMID: 26516156
- Alisertib and TAK-228 in Participants with Human Papilloma Virus (HPV) Associated Malignancies NCT02812056, 2016.
- Martin, D.; Fallaha, S.; Proctor, M.; Stevenson, A.; Perrin, L.; McMillan, N.; Gabrielli, B. Inhibition of aurora A and aurora B is required for the sensitivity of HPV-driven cervical cancers to aurora kinase inhibitors. Mol. Cancer Ther., 2017, 16(9), 1934-1941. doi: 10.1158/1535-7163.MCT-17-0159 PMID: 28522591
- Shaikh, M.H.; Idris, A.; Johnson, N.W.; Fallaha, S.; Clarke, D.T.W.; Martin, D.; Morgan, I.M.; Gabrielli, B.; McMillan, N.A.J. Aurora kinases are a novel therapeutic target for HPV-positive head and neck cancers. Oral Oncol., 2018, 86, 105-112. doi: 10.1016/j.oraloncology.2018.09.006 PMID: 30409290
- Yumol, J.; Gabrielli, B.; Tayyar, Y.; McMillan, N.A.; Idris, A. Smart drug combinations for cervical cancer: dual targeting of Bcl-2 family of proteins and aurora kinases. Am. J. Cancer Res., 2020, 10(10), 3406-3414. PMID: 33163279
- Banerjee, N.S.; Moore, D.; Parker, C.J.; Broker, T.R.; Chow, L.T. Targeting DNA damage response as a strategy to treat HPV infections. Int. J. Mol. Sci., 2019, 20(21), 5455. doi: 10.3390/ijms20215455 PMID: 31683862
- Bazzaro, M.; Anchoori, R.K.; Mudiam, M.K.R.; Issaenko, O.; Kumar, S.; Karanam, B.; Lin, Z.; Isaksson Vogel, R.; Gavioli, R.; Destro, F.; Ferretti, V.; Roden, R.B.S.; Khan, S.R. α,β-Unsaturated carbonyl system of chalcone-based derivatives is responsible for broad inhibition of proteasomal activity and preferential killing of human papilloma virus (HPV) positive cervical cancer cells. J. Med. Chem., 2011, 54(2), 449-456. doi: 10.1021/jm100589p PMID: 21186794
- Anchoori, R.K.; Karanam, B.; Peng, S.; Wang, J.W.; Jiang, R.; Tanno, T.; Orlowski, R.Z.; Matsui, W.; Zhao, M.; Rudek, M.A.; Hung, C.; Chen, X.; Walters, K.J.; Roden, R.B.S. A bis-benzylidine piperidone targeting proteasome ubiquitin receptor RPN13/ADRM1 as a therapy for cancer. Cancer Cell, 2013, 24(6), 791-805. doi: 10.1016/j.ccr.2013.11.001 PMID: 24332045
- Ren, B.; Ablise, M.; Yang, X.; Liao, B.; Yang, Z. Synthesis and biological evaluation of α-methyl-chalcone for anti-cervical cancer activity. Med. Chem. Res., 2017, 26(9), 1871-1883. doi: 10.1007/s00044-017-1891-0
- Li, C.; Johnson, D.E. Liberation of functional p53 by proteasome inhibition in human papilloma virus-positive head and neck squamous cell carcinoma cells promotes apoptosis and cell cycle arrest. Cell Cycle, 2013, 12(6), 923-934. doi: 10.4161/cc.23882 PMID: 23421999
- Kim, J.E.E.E.U.N.; Lee, J.I.I.N.; Jin, D.H.; Lee, W.J.; Park, G.B.; Kim, S.; Kim, Y.S.; Wu, T.C.; Hur, D.Y.; Kim, D. Sequential treatment of HPV E6 and E7-expressing TC-1 cells with bortezomib and celecoxib promotes apoptosis through p-p38 MAPK-mediated downregulation of cyclin D1 and CDK2. Oncol. Rep., 2014, 31(5), 2429-2437. doi: 10.3892/or.2014.3082 PMID: 24627094
- Study of Celebrex (Celecoxib) in Patients with Recurrent Respiratory Papillomatosis. NCT00571701, 2017.
- Palefsky, J. Biology of HPV in HIV Infection. Adv. Dent. Res., 2006, 19(1), 99-105. doi: 10.1177/154407370601900120 PMID: 16672559
- Hampson, L.; Kitchener, H.C.; Hampson, I.N. Specific HIV protease inhibitors inhibit the ability of HPV16 E6 to degrade p53 and selectively kill E6-dependent cervical carcinoma cells in vitro. Antivir. Ther., 2006, 11(6), 813-826. doi: 10.1177/135965350601100607 PMID: 17310826
- Kim, D.H.; Jarvis, R.M.; Xu, Y.; Oliver, A.W.; Allwood, J.W.; Hampson, L.; Hampson, I.N.; Goodacre, R. Combining metabolic fingerprinting and footprinting to understand the phenotypic response of HPV16 E6 expressing cervical carcinoma cells exposed to the HIV anti-viral drug lopinavir. Analyst (Lond.), 2010, 135(6), 1235-1244. doi: 10.1039/b923046g PMID: 20390218
- Kim, D.H.; Jarvis, R.M.; Allwood, J.W.; Batman, G.; Moore, R.E.; Marsden-Edwards, E.; Hampson, L.; Hampson, I.N.; Goodacre, R. Raman chemical mapping reveals site of action of HIV protease inhibitors in HPV16 E6 expressing cervical carcinoma cells. Anal. Bioanal. Chem., 2010, 398(7-8), 3051-3061. doi: 10.1007/s00216-010-4283-6 PMID: 20957472
- Batman, G.; Oliver, A.W.; Zehbe, I.; Richard, C.; Hampson, L.; Hampson, I.N. Lopinavir up-regulates expression of the antiviral protein ribonuclease L in human papillomavirus-positive cervical carcinoma cells. Antivir. Ther., 2011, 16(4), 515-525. doi: 10.3851/IMP1786 PMID: 21685539
- Brennan-Laun, S.E.; Ezelle, H.J.; Li, X.L.; Hassel, B.A. RNase-L control of cellular mRNAs: roles in biologic functions and mechanisms of substrate targeting. J. Interferon Cytokine Res., 2014, 34(4), 275-288. doi: 10.1089/jir.2013.0147 PMID: 24697205
- Zehbe, I.; Richard, C.; Lee, K.F.; Campbell, M.; Hampson, L.; Hampson, I.N. Lopinavir shows greater specificity than zinc finger ejecting compounds as a potential treatment for human papillomavirus-related lesions. Antiviral Res., 2011, 91(2), 161-166. doi: 10.1016/j.antiviral.2011.05.016 PMID: 21669231
- Park, S.; Auyeung, A.; Lee, D.L.; Lambert, P.F.; Carchman, E.H.; Sherer, N.M. HIV-1 protease inhibitors slow HPV16-driven cell proliferation through targeted depletion of viral E6 and E7 oncoproteins. Cancers (Basel), 2021, 13(5), 949. doi: 10.3390/cancers13050949 PMID: 33668328
- Bandiera, E.; Todeschini, P.; Romani, C.; Zanotti, L.; Erba, E.; Colmegna, B.; Bignotti, E.; Santin, A.D.; Sartori, E.; Odicino, F.E.; Pecorelli, S.; Tassi, R.A.; Ravaggi, A. The HIV-protease inhibitor saquinavir reduces proliferation, invasion and clonogenicity in cervical cancer cell lines. Oncol. Lett., 2016, 12(4), 2493-2500. doi: 10.3892/ol.2016.5008 PMID: 27698818
- Davis, M-A.; Delaney, J.R.; Patel, C.B.; Storgard, R.; Stupack, D.G. Nelfinavir is effective against human cervical cancer cells in vivo: a potential treatment modality in resource-limited settings. Drug Des. Devel. Ther., 2016, 10, 1837-1846. PMID: 27330277
- Xia, C.; Chen, R.; Chen, J.; Qi, Q.; Pan, Y.; Du, L.; Xiao, G.; Jiang, S. Combining metformin and nelfinavir exhibits synergistic effects against the growth of human cervical cancer cells and xenograft in nude mice. Sci. Rep., 2017, 7(1), 43373. doi: 10.1038/srep43373 PMID: 28252027
- Xia, C.; He, Z.; Liang, S.; Chen, R.; Xu, W.; Yang, J.; Xiao, G.; Jiang, S. Metformin combined with nelfinavir induces SIRT3/mROS-dependent autophagy in human cervical cancer cells and xenograft in nude mice. Eur. J. Pharmacol., 2019, 848, 62-69. doi: 10.1016/j.ejphar.2019.01.045 PMID: 30695683
- Xia, C.; Yang, F.; He, Z.; Cai, Y. iTRAQ-based quantitative proteomic analysis of the inhibition of cervical cancer cell invasion and migration by metformin. Biomed. Pharmacother., 2020, 123, 109762. doi: 10.1016/j.biopha.2019.109762 PMID: 31864213
- Xia, C.; Liu, C.; He, Z.; Cai, Y.; Chen, J. Metformin inhibits cervical cancer cell proliferation by modulating PI3K/Akt-induced major histocompatibility complex class I-related chain A gene expression. J. Exp. Clin. Cancer Res., 2020, 39(1), 127. doi: 10.1186/s13046-020-01627-6 PMID: 32631421
- Chen, Y.H.; Yang, S.F.; Yang, C.K.; Tsai, H.D.; Chen, T.H.; Chou, M.C.; Hsiao, Y.H. Metformin induces apoptosis and inhibits migration by activating the AMPK/p53 axis and suppressing PI3K/AKT signaling in human cervical cancer cells. Mol. Med. Rep., 2020, 23(1), 88. doi: 10.3892/mmr.2020.11725 PMID: 33236135
- Hoppe-Seyler, K.; Herrmann, A.L.; Däschle, A.; Kuhn, B.J.; Strobel, T.D.; Lohrey, C.; Bulkescher, J.; Krijgsveld, J.; Hoppe-Seyler, F. Effects of metformin on the virus/host cell crosstalk in human papillomavirus‐positive cancer cells. Int. J. Cancer, 2021, 149(5), 1137-1149. doi: 10.1002/ijc.33594 PMID: 33844847
- Donalisio, M.; Massari, S.; Argenziano, M.; Manfroni, G.; Cagno, V.; Civra, A.; Sabatini, S.; Cecchetti, V.; Loregian, A.; Cavalli, R.; Lembo, D.; Tabarrini, O. Ethyl 1,8-naphthyridone-3-carboxylates downregulate human papillomavirus-16 E6 and E7 oncogene expression. J. Med. Chem., 2014, 57(13), 5649-5663. doi: 10.1021/jm500340h PMID: 24905115
- Cardone, G.; Moyer, A.L.; Cheng, N.; Thompson, C.D.; Dvoretzky, I.; Lowy, D.R.; Schiller, J.T.; Steven, A.C.; Buck, C.B.; Trus, B.L. Maturation of the human papillomavirus 16 capsid. MBio, 2014, 5(4), e01104-e01114. doi: 10.1128/mBio.01104-14 PMID: 25096873
- de Villiers, E.M.; Fauquet, C.; Broker, T.R.; Bernard, H.U.; zur Hausen, H. Classification of papillomaviruses. Virology, 2004, 324(1), 17-27. doi: 10.1016/j.virol.2004.03.033 PMID: 15183049
- Buck, C.B.; Day, P.M.; Trus, B.L. The papillomavirus major capsid protein L1. Virology, 2013, 445(1-2), 169-174. doi: 10.1016/j.virol.2013.05.038 PMID: 23800545
- Wang, J.W.; Roden, R.B.S. L2, the minor capsid protein of papillomavirus. Virology, 2013, 445(1-2), 175-186. doi: 10.1016/j.virol.2013.04.017 PMID: 23689062
- Zheng, D.D.; Fu, D.Y.; Wu, Y.; Sun, Y.L.; Tan, L.L.; Zhou, T.; Ma, S.Q.; Zha, X.; Yang, Y.W. Efficient inhibition of human papillomavirus 16 L1 pentamer formation by a carboxylatopillarene and a p-sulfonatocalixarene. Chem. Commun. (Camb.), 2014, 50(24), 3201-3203. doi: 10.1039/c3cc49789e PMID: 24522285
- Fu, D.Y.; Lu, T.; Liu, Y.X.; Li, F.; Ogden, M.I.; Wang, Y.; Wu, Y.; Mocerino, M. Enantioselective inhibition of human papillomavirus L1 pentamer formation by chiral‐proline modified calix4arenes: Targeting the protein interface. ChemistrySelect, 2016, 1(19), 6243-6249. doi: 10.1002/slct.201601467
- Goh, C.Y.; Fu, D.Y.; Duncan, C.L.; Tinker, A.; Li, F.; Mocerino, M.; Ogden, M.I.; Wu, Y. The inhibitory properties of acidic functionalised calix4arenes on human papillomavirus pentamer formation. Supramol. Chem., 2020, 32(5), 345-353. doi: 10.1080/10610278.2020.1779930
- Selinka, H.C.; Florin, L.; Patel, H.D.; Freitag, K.; Schmidtke, M.; Makarov, V.A.; Sapp, M. Inhibition of transfer to secondary receptors by heparan sulfate-binding drug or antibody induces noninfectious uptake of human papillomavirus. J. Virol., 2007, 81(20), 10970-10980. doi: 10.1128/JVI.00998-07 PMID: 17686860
- Surviladze, Z.; Dziduszko, A.; Ozbun, M.A. Essential roles for soluble virion-associated heparan sulfonated proteoglycans and growth factors in human papillomavirus infections. PLoS Pathog., 2012, 8(2), e1002519. doi: 10.1371/journal.ppat.1002519 PMID: 22346752
- Müller, K.H.; Spoden, G.A.; Scheffer, K.D.; Brunnhöfer, R.; De Brabander, J.K.; Maier, M.E.; Florin, L.; Muller, C.P. Inhibition by cellular vacuolar ATPase impairs human papillomavirus uncoating and infection. Antimicrob. Agents Chemother., 2014, 58(5), 2905-2911. doi: 10.1128/AAC.02284-13 PMID: 24614368
- Karanam, B.; Peng, S.; Li, T.; Buck, C.; Day, P.M.; Roden, R.B.S. Papillomavirus infection requires gamma secretase. J. Virol., 2010, 84(20), 10661-10670. doi: 10.1128/JVI.01081-10 PMID: 20702627
- Huang, H.S.; Buck, C.B.; Lambert, P.F. Inhibition of gamma secretase blocks HPV infection. Virology, 2010, 407(2), 391-396. doi: 10.1016/j.virol.2010.09.002 PMID: 20875908
- Kwak, K.; Jiang, R.; Wang, J.W.; Jagu, S.; Kirnbauer, R.; Roden, R.B.S. Impact of inhibitors and L2 antibodies upon the infectivity of diverse alpha and beta human papillomavirus types. PLoS One, 2014, 9(5), e97232. doi: 10.1371/journal.pone.0097232 PMID: 24816794
- Richards, R.M.; Lowy, D.R.; Schiller, J.T.; Day, P.M. Cleavage of the papillomavirus minor capsid protein, L2, at a furin consensus site is necessary for infection. Proc. Natl. Acad. Sci. USA, 2006, 103(5), 1522-1527. doi: 10.1073/pnas.0508815103 PMID: 16432208
- Huang, H.S.; Pyeon, D.; Pearce, S.M.; Lank, S.M.; Griffin, L.M.; Ahlquist, P.; Lambert, P.F. Novel antivirals inhibit early steps in HPV infection. Antiviral Res., 2012, 93(2), 280-287. doi: 10.1016/j.antiviral.2011.12.007 PMID: 22197636
- Walhart, T.; Isaacson-Wechsler, E.; Ang, K.H.; Arkin, M.; Tugizov, S.; Palefsky, J.M. A cell-based Renilla luminescence reporter plasmid assay for high-throughput screening to identify novel FDA-approved drug inhibitors of HPV-16 infection. SLAS Discov., 2020, 25(1), 79-86. doi: 10.1177/2472555219860771 PMID: 31361520
Supplementary files
