Human papillomavirus (HPV) is known as the main cause of cervical cancer. Most sexually active women and men might be high risk infected by HPV. In Indonesia, HPV-16 and 18 types are equally common in the general population associated with cervical cancer. HPV-52 is the most prevalent type in the general population worldwide. Some natural products have been identified as promising sources as inhibitor agents for treatment and prevention of cancers in recent years. Indonesia is abundant of original plants with bioactive compounds that play role as anticancer, such as red fruit, turmeric, god's crown, ground cherry and white turmeric. The aim of this research is to structure-based screen the interaction between protein E6 from HPV-16, 18 and 52 strains with natural compounds through molecular docking. Out of five natural compounds that we studied, we found the highest binding energy to interact with E6 HPV-16 is daphnoretin (-6.8 kcal/mol), HPV-18 and 52 is ?-cryptoxanthin -6.5 kcal/mol and -6.6 kcal/mol. Molecular dynamics simulations provide a platform for capturing the structures, motions, and interactions of biological macromolecules in full atomic details. The accuracy of such simulations, however, is critically dependent on the force field the mathematical model used to approximate the atomic-level forces acting on the simulated molecular system. The results suggest that the third profile of protein E6 HPV-18 and 52 tend to be stable, while E6 HPV-16 was not stable, this might be due to the differences in the ligand interaction.
Vivitri D. Prasasty, Ignatia Eveline, Ekaristy J. Noya
HR HPV, E6 Oncoprotein, Natural Inhibitors, Molecular Docking
- International Agency for Research on Cancer. Globocan 2008 fast stats Internet] Lyon, France: International Agency for Research on Cancer; 2010.
- World Health Organization. Cervical cancer screening in developing countries: report of a WHO consultation Internet] Geneva: World Health Organization; 2002.
- Ministry of Health of the Republic of Indonesia; Indonesian Pathology Association; The Indonesian Cancer Foundation. Histopathological data of cancer in Indonesia 2006. Jakarta: Ministry of Health of the Republic of Indonesia; 2006.
- M.F. Aziz. 2009. Gynecological cancer in Indonesia. J. Gynecol Oncol. 20:8–10.
- J. Doorbar, N. Egawa, H. Griffin, C. Kranjec, I. Murakami. 2015. Human papillomavirus molecular biology and disease association. Reviews in medical virology 25.S1 (2015): 2-23.
- Center for Disease Control and Prevention. The link between HPV and cancer. 2015.
- J.N.I. Vet, M.A. de Boer, B. E. W. M. van den Akker, B. Siregar, Lisnawati, S. Budiningsih, D. Tyasmorowati, Moestikaningsih, S. Cornain, A.A.W. Peters, G.J. Fleuren. 2008. Prevalence of human papillomavirus in Indonesia: a population-based study in three regions. British journal of cancer. 99.1: 214-218.
- G.J. Fleuren, J.N.I. Vet, M.A. de Boer. 2008. Prevalence of human papillomavirus in Indonesia: a population-based study in three regions. British Journal Cancer . 99: 214-218.
- F. Fehrmann, , D. J. Klumpp, L. A. Laimins. 2003. Human papillomavirus type 31 E5 protein supports cell cycle progression and activates late viral functions upon epithelial differentiation. J. Virol. 77:2819–2831.
- Indraswati, Bestantia. 2005. Kanker Leher Rahim, Pembunuh No.1 Para Wanita di Indonesia dalam: Sehat. No.6 / Vol.3. Jakarta: PT Mitra Media Prima.
- C. Dolinsky, C. Hill-Kayser. 2008. Cervical Cancer : The Basics. Trustees of the University of Pennsylvania.
- Ratnawati, Hana, W. Wahyu, K.J. Diana, S. Sylvia. 2008. Cytotoxic activity of Buah Merah fractions (Pandanus conoideus Lam) towards cervical cancer cell in HeLa Cells Culture. Proceeding of The International Seminar on Chemistry 2008 (pp. 317-320).
- Basnet, Natasa Skalko and Purusotam. 2011. Curcumin: An anti-inflammatory molecule from a curry spice on the path to cancer treatment.
- Radji, Maksum, A. Hendri, H. Yahdiana, I. Cosphiadi. 2010. Uji sitotoksisitas buah merah, mahkota dewa dan temu putih terhadap sel kanker serviks.
- C.C. Baker, W.C. Phelps, V. Lindgren, M. J. Braun, M. A. Gonda, P. M. Howley. 1987. Structural and translational analysis of human papillomavirus type 16 sequences in cervical carcinoma cell lines. J. Virol. 61:962–971.
- K. Seedorf, G. Krammer, M. Durst, S. Suhai, W.G. Rowekamp. 1985. Human papillomavirus type 16 DNA sequence. Virology 145(1): 181-185.
- S.T. Cole, O. Danos. 1987. Nucleotide sequence and comparative analysis of the human papillomavirus type 18 genome. Phylogeny of papillomaviruses and repeated structure of the E6 and E7 gene products. J. Mol. Biol. 193:599-608.
- H. Delius, B. Hofmann. 1994. Primer-directed sequencing of human papillomavirus types. Curr. Top. Microbiol. Immunol. 186:13-31.
- K. Arnold, L. Bordoli, J. Kopp, T. Schwede. 2006. The SWISS-MODEL workspace: A web-based environment for protein structure homology modelling. Bioinformatics 22: 195-201. DOI: 10.1093/bioinformatics/bti770.
- R.A. Laskowski, M.W. MacArthur, D.S. Moss, Thornton JM. PROCHECK : a program to check the stereochemical quality of protein structures. J Appl Crystallogr 1993;26:283-291.
- V. Lisdawati, S. Wiryowidagdo, L. B. S. Kardono. 2007. Lignan, isolasi dan elusidasi struktur senyawa, dan asam. "lemak dari ekstrak daging buah phaleria macrocarpa. Bul. Penel. Kesehatan. 35(2): 115-124.
- E. M. Sutrisna. 2007. Potensi Sitotoksik Tanaman Ceplukan (Physalis Angulata L) Terhadap Sel Hela Cytotoxic Effects Of Physallis Angulata Plant On Hela Cell Line Cells. Pharmacon, 8(1): 1–6.
- R. Lobo, K. S. Prabhu, A. Shirwaikar, A. Shirwaikar. 2009. Curcuma zedoaria Rosc. (white turmeric): a review of its chemical, pharmacological and ethnomedicinal properties. Journal of Pharmacy and Pharmacology. 61(1): Pages 13–21.
- O. Trott, A. J. Olson. 2010. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading, Journal of Computational Chemistry 31: 455-461.
- A.L. Morris, M.W. MacArthur, E.G. Hutchinson,
- J.M. Thornton. 1992. Chemical quality of protein structure coordinates. Proteins Struct Funct Genet 12:345-364.
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||Volume 3 | Issue 2 | March-April - 2017
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Cite This Article
Vivitri D. Prasasty, Ignatia Eveline, Ekaristy J. Noya, "Potential Natural Inhibitor Bioactivities against High-Risk HPV-16, HPV-18 and HPV-52 of E6 Oncoprotein through Molecular Docking", International Journal of Scientific Research in Science, Engineering and Technology(IJSRSET), Print ISSN : 2395-1990, Online ISSN : 2394-4099, Volume 3, Issue 2, pp.39-45, March-April-2017.
URL : http://ijsrset.com/IJSRSET1731114.php