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http://dx.doi.org/10.5808/GI.2015.13.2.60

In Silico Docking to Explicate Interface between Plant-Originated Inhibitors and E6 Oncogenic Protein of Highly Threatening Human Papillomavirus 18  

Kumar, Satish (Bioinformatics Centre & Biochemistry, Mahatma Gandhi Institute of Medical Sciences)
Jena, Lingaraja (Bioinformatics Centre & Biochemistry, Mahatma Gandhi Institute of Medical Sciences)
Sahoo, Maheswata (Bioinformatics Centre & Biochemistry, Mahatma Gandhi Institute of Medical Sciences)
Kakde, Mrunmayi (Bioinformatics Centre & Biochemistry, Mahatma Gandhi Institute of Medical Sciences)
Daf, Sangeeta (Obstetrics & Gynaecology, Datta Meghe Institute of Medical Sciences (Deemed University))
Varma, Ashok K. (Advanced Centre for Treatment, Research & Education in Cancer)
Publication Information
Genomics & Informatics / v.13, no.2, 2015 , pp. 60-67 More about this Journal
Abstract
The leading cause of cancer mortality globally amongst the women is due to human papillomavirus (HPV) infection. There is need to explore anti-cancerous drugs against this life-threatening infection. Traditionally, different natural compounds such as withaferin A, artemisinin, ursolic acid, ferulic acid, (-)-epigallocatechin-3-gallate, berberin, resveratrol, jaceosidin, curcumin, gingerol, indol-3-carbinol, and silymarin have been used as hopeful source of cancer treatment. These natural inhibitors have been shown to block HPV infection by different researchers. In the present study, we explored these natural compounds against E6 oncoprotein of high risk HPV18, which is known to inactivate tumor suppressor p53 protein. E6, a high throughput protein model of HPV18, was predicted to anticipate the interaction mechanism of E6 oncoprotein with these natural inhibitors using structure-based drug designing approach. Docking analysis showed the interaction of these natural inhibitors with p53 binding site of E6 protein residues 108-117 (CQKPLNPAEK) and help reinstatement of normal p53 functioning. Further, docking analysis besides helping in silico validations of natural compounds also helped elucidating the molecular mechanism of inhibition of HPV oncoproteins.
Keywords
human papillomavirus 18; molecular docking; neoplasms; plant products;
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1 Hoory T, Monie A, Gravitt P, Wu TC. Molecular epidemiology of human papillomavirus. J Formos Med Assoc 2008;107:198-217.   DOI
2 de Martel C, Ferlay J, Franceschi S, Vignat J, Bray F, Forman D, et al. Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. Lancet Oncol 2012;13:607-615.   DOI
3 Bruni L, Barrionuevo-Rosas L, Albero G, Aldea M, Serrano B, Valencia S, et al. ICO Information Centre on HPV and Cancer (HPV Information Centre). Human Papillomavirus and Related Diseases in the World. Summary Report. Barcelona: ICO Information Centre on HPV and Cancer, 2014. Accessed 2014 Dec 18. Available from: http://www.hpvcentre.net/statistics/reports/XWX.pdf.
4 Guan P, Howell-Jones R, Li N, Bruni L, de Sanjose S, Franceschi S, et al. Human papillomavirus types in 115,789 HPV-positive women: a meta-analysis from cervical infection to cancer. Int J Cancer 2012;131:2349-2359.   DOI
5 Chaturvedi AK. Beyond cervical cancer: burden of other HPV-related cancers among men and women. J Adolesc Health 2010;46(4 Suppl):S20-S26.
6 Scheffner M, Munger K, Byrne JC, Howley PM. The state of the p53 and retinoblastoma genes in human cervical carcinoma cell lines. Proc Natl Acad Sci U S A 1991;88:5523-5527.   DOI
7 Hubbert NL, Sedman SA, Schiller JT. Human papillomavirus type 16 E6 increases the degradation rate of p53 in human keratinocytes. J Virol 1992;66:6237-6241.
8 Bharti AC, Shukla S, Mahata S, Hedau S, Das BC. Anti-human papillomavirus therapeutics: facts and future. Indian J Med Res 2009;130:296-310.
9 Gordaliza M. Natural products as leads to anticancer drugs. Clin Transl Oncol 2007;9:767-776.   DOI
10 Sagar SM, Yance D, Wong RK. Natural health products that inhibit angiogenesis: a potential source for investigational new agents to treat cancer: part 1. Curr Oncol 2006;13:14-26.
11 Yuan F, Chen DZ, Liu K, Sepkovic DW, Bradlow HL, Auborn K. Anti-estrogenic activities of indole-3-carbinol in cervical cells: implication for prevention of cervical cancer. Anticancer Res 1999;19:1673-1680.
12 Novotny L, Vachalkova A, Biggs D. Ursolic acid: an anti-tumorigenic and chemopreventive activity. Minireview. Neoplasma 2001;48:241-246.
13 Zoberi I, Bradbury CM, Curry HA, Bisht KS, Goswami PC, Roti Roti JL, et al. Radiosensitizing and anti-proliferative effects of resveratrol in two human cervical tumor cell lines. Cancer Lett 2002;175:165-173.   DOI
14 Bava SV, Puliappadamba VT, Deepti A, Nair A, Karunagaran D, Anto RJ. Sensitization of taxol-induced apoptosis by curcumin involves down-regulation of nuclear factor-kappaB and the serine/threonine kinase Akt and is independent of tubulin polymerization. J Biol Chem 2005;280:6301-6308.   DOI
15 Singh M, Singh N. Molecular mechanism of curcumin induced cytotoxicity in human cervical carcinoma cells. Mol Cell Biochem 2009;325:107-119.   DOI
16 Ahn WS, Yoo J, Huh SW, Kim CK, Lee JM, Namkoong SE, et al. Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions. Eur J Cancer Prev 2003;12:383-390.   DOI
17 Manju V, Nalini N. Chemopreventive efficacy of ginger, a naturally occurring anticarcinogen during the initiation, post-initiation stages of 1,2 dimethylhydrazine-induced colon cancer. Clin Chim Acta 2005;358:60-67.   DOI
18 Lee HG, Yu KA, Oh WK, Baeg TW, Oh HC, Ahn JS, et al. Inhibitory effect of jaceosidin isolated from Artemisia argyi on the function of E6 and E7 oncoproteins of HPV 16. J Ethnopharmacol 2005;98:339-343.   DOI
19 Buck CB, Thompson CD, Roberts JN, Muller M, Lowy DR, Schiller JT. Carrageenan is a potent inhibitor of papillomavirus infection. PLoS Pathog 2006;2:e69.   DOI
20 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;32:1309-1315.   DOI
21 Mahata S, Bharti AC, Shukla S, Tyagi A, Husain SA, Das BC. 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;10:39.   DOI
22 Karthikeyan S, Kanimozhi G, Prasad NR, Mahalakshmi R. Radiosensitizing effect of ferulic acid on human cervical carcinoma cells in vitro. Toxicol In Vitro 2011;25:1366-1375.   DOI
23 Yu HC, Chen LJ, Cheng KC, Li YX, Yeh CH, Cheng JT. Silymarin inhibits cervical cancer cell through an increase of phosphatase and tensin homolog. Phytother Res 2012;26:709-715.   DOI
24 Munagala R, Kausar H, Munjal C, Gupta RC. Withaferin A induces p53-dependent apoptosis by repression of HPV oncogenes and upregulation of tumor suppressor proteins in human cervical cancer cells. Carcinogenesis 2011;32:1697-1705.   DOI
25 Hu CJ, Zhou L, Cai Y. Dihydroartemisinin induces apoptosis of cervical cancer cells via upregulation of RKIP and downregulation of bcl-2. Cancer Biol Ther 2014;15:279-288.   DOI
26 Sharada AC, Solomon FE, Devi PU, Udupa N, Srinivasan KK. Antitumor and radiosensitizing effects of withaferin A on mouse Ehrlich ascites carcinoma in vivo. Acta Oncol 1996;35:95-100.   DOI
27 Bargagna-Mohan P, Hamza A, Kim YE, Khuan Abby Ho Y, Mor-Vaknin N, Wendschlag N, et al. The tumor inhibitor and antiangiogenic agent withaferin A targets the intermediate filament protein vimentin. Chem Biol 2007;14:623-634.   DOI
28 Kelley LA, Sternberg MJ. Protein structure prediction on the Web: a case study using the Phyre server. Nat Protoc 2009;4:363-371.   DOI
29 Krieger E, Joo K, Lee J, Lee J, Raman S, Thompson J, et al. Improving physical realism, stereochemistry, and side-chain accuracy in homology modeling: four approaches that performed well in CASP8. Proteins 2009;77 Suppl 9:114-122.   DOI
30 Krivov GG, Shapovalov MV, Dunbrack RL Jr. Improved prediction of protein side-chain conformations with SCWRL4. Proteins 2009;77:778-795.   DOI
31 Laskowski RA, MacArthur MW, Moss DS, Thornton JM. PROCHECK: a program to check the stereochemical quality of protein structures. J Appl Crystallogr 1993;26:283-291.   DOI
32 Wiederstein M, Sippl MJ. ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Res 2007;35:W407-W410.   DOI
33 Wallner B, Elofsson A. Can correct protein models be identified? Protein Sci 2003;12:1073-1086.   DOI
34 Eisenberg D, Luthy R, Bowie JU. VERIFY3D: assessment of protein models with three-dimensional profiles. Methods Enzymol 1997;277:396-404.   DOI
35 Wang Y, Xiao J, Suzek TO, Zhang J, Wang J, Bryant SH. PubChem: a public information system for analyzing bioactivities of small molecules. Nucleic Acids Res 2009;37:W623-W633.   DOI
36 Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, et al. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J Comput Chem 2009;30:2785-2791.   DOI
37 Kumar S, Jena L, Galande S, Daf S, Mohod K, Varma AK. Elucidating molecular interactions of natural inhibitors with HPV-16 E6 oncoprotein through docking analysis. Genomics Inform 2014;12:64-70.   DOI
38 Crook T, Tidy JA, Vousden KH. Degradation of p53 can be targeted by HPV E6 sequences distinct from those required for p53 binding and trans-activation. Cell 1991;67:547-556.   DOI
39 Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol 1990;215:403-410.   DOI
40 Muthukala B, Sivakumari K, Ashok K. In silico docking of Quercetin compound against the Hela cell line proteins. Int J Curr Pharm Res 2015;7:13-16.
41 Mamgain S, Sharma P, Pathak RK, Baunthiyal M. Computer aided screening of natural compounds targeting the E6 protein of HPV using molecular docking. Bioinformation 2015;11:236-242.   DOI
42 Kotadiya R, Georrge JJ. In silico approach to identify putative drugs from natural products for human papillomavirus (HPV) which cause cervical cancer. Life Sci Leafl 2015;63:1-13.
43 Samant LR, Sangar VC, Chaudhary S, Chowdhary A. In silico molecular interactions of HIV antiviral drugs against HPV type 18 E6 protein. World J Pharm Pharm Sci 2015;4:1056-1066.