To know the role of 10-hydroxycamptothecine in anticancer activity, we have selected 45 cancer proteins for in silico study. 10% of the world population death is from different types of cancer and it indicates need of better therapeutic against which are less toxic. 10-hydroxycamptothecine was identified from different plants and endophytic fungal species and exhibiting antioxidant, antimicrobial, anti-inflammatory and anticancer activities. The present research was aimed to know interaction studies of 10-hydroxycamptothecine with various cancers virulent proteins using computer aided virtual screening using iGEMDOCK. The ADMET test clarifies its drug like properties. In present study, selected 45 different cancers proteins were selected based on virulent functions for interaction studies and was identified based on binding energy. The 10-hydroxycamptothecine have shown highest binding energy to cancer virulent proteins viz., BCl-Xl BAK (-100.19 kcal/mol), small cell lung cancer (-115.4 kcal/mol), BAX (-108 kcal/mol), reps1 EH domain (-107.94 kcal/mol), Hodgkin lymphoma (-107.35 kcal/mol), MCF (-94.8 kcal/mol), two ribosome-inactivating proteins (-107.51 kcal/mol), epidermal growth factor (EGF) (-99.9 kcal/mol), Malignant pleural mesothelioma (-94 kcal/mol), MCF-9-EGFR tyrosine kinase (-102.9 kcal/mol), CDK4 in complex with a d-type cyclin (-102.2 kcal/mol), Gastric cancer (-98.01 kcal/mol), Ovarian Cancer (-109 kcal/mol), Oral cancer (-93.5 kcal/mol), HER-2 (-100.28 kcal/mol), BCl-2 (-101.2 kcal/mol), BCl-2 protein (-111.8 kcal/mol), BH3 domain (-102 kcal/mol), BID (-94 kcal/mol), Bcl-2 alpha beta-1 LINEAR complex (-94.8 kcal/mol), MCl-1 (-97.8 kcal/mol), topoisomerase (-101.29 kcal/mol), Topoisomerase 2A (-104.79 kcal/mol), caspase -3 (-118.9 kcal/mol), topo 4 (-103.35 kcal/mol), caspase 9 (-94.1 kcal/mol). The ligand has more binding energy growth factors and receptors, gastric, oral, ovarian cancer and MCl-1 proteins. BCl-2 and its proteins have more attracted to ligand. The ligand has ability to bind topoisomerase, 2A and caspase 3 and 9. The study results concluded that 10-hydroxycamptothecine has higher interacting properties to different cancer proteins and enzymes and therefore it can be used as novel inhibitory agents against different cancers. Molecular docking studies strongly support the experimental results and results of the present data concluded that 10-hydroxycamptothecine clearly shows how it interacts with different cancer proteins and cancer enzymes can lead as potential nontoxic anticancer agent.
10-Hydroxycamptothecine, Anticancer Agent, Virtual Screening, Cancer Proteins, Cancer Enzymes
Lin, L. Z; Cordell, G. A. (1990). 13C-NMR assignments of camptothecine and 10-hydroxycampthocine, J Natural Prod, 53 (1): 186-189.
Hsiang, C. Y; Ho, T. Y; Lin, C. H; Wu, K; Chang, T. J. (1996). Analysis of upregulated cellular genes in pseudorabies virus infection: use of mRNA differential display. J Virol Methods, 62: 11–19.
Pommier, Y. (2006). Topoisomerase I inhibitors: camptothecines and beyond, Nature Rev Cancer, 6: 789–802.
Li, P; Chen, Q; Yu, F; Xie, X; Wang, S. (2015). Simultaneous determination of camptothecin and 10-hydroxycamptothecine in the Camptotheca acuminata, its medicinal preparation and in rat plasma by liquid chromatography with fluorescence detection, Biomed Chromatography, 29 (10): 1522-1526.
Sun, Y; Zhao, H; Lin, F; Cai, X; Tang, X; Yao, Y. (2007). The short-time effects of chemotherapy with combinations of hydroxycamptothecine and oxaliplatin in treatment of advanced colorectal cancer, The Chinese-German J Clin Onc, 6 (1): 40–43.
Sun, Y; Wang, L; Sun, S; Liu, B; Wu, N; Cao, X. (2008). The effect of 10-hydroxycamptothecine in preventing fibroblast proliferation and epidural scar adhesion after laminectomy in rats, Eur J Pharm, 593 (1-3): 44-48.
Shao, S. L; Zhang, W. W; Zhao, W; Wu, G. H. (2012). Apoptosis of human leukemia cell line K562 cells induced by hydroxycamptothecine, Adv Mater Res, 535-537: 2420-2424.
Nie, F; Cao, J; Tong, J; Zhu, M; Gao, Y; Ran, Z. (2015). Role of Raf-kinase inhibitor protein in colorectal cancer and its regulation by hydroxycamptothecine, J Biomed Sci, 5: 22: 56.
Covey, J. M; Jaxel, C; Kohn, K. W. (1989). Cancer Res, 48: 5016.
Hsiang, Y. H; Lihou, M. G; Liu, L. F. (1989). Cancer Res, 49: 5077.
Tang, W; Zhang, Y; Oian, C; Yuan, Z; Du, J. (2012). Induction and mechanism of apoptosis by hydroxycamptothecin in human Tenon's capsule fibroblasts, Invest Ophthal Visual Sci, 53: 4874-4880.
Aggarwal, S; Takada, Y; Singh, S; Myers, J. N; Aggarwal, B. (2004). Inhibition of growth and survival of human head and neck squamous cell carcinoma cells by curcumin via modulation of nuclear factor-kB signalling, Int J Cancer, 111: 679-692.
Kanehisa, M; Goto, S. (2000). KEGG: Kyoto encyclopedia of genes and genomes, Nucl Acid Res, 28: 27-30.
Berman, H. M; Westbrook, J; Fengm Z; Gilliland, G; Bhat, T. N; Weissig, H; Shindyalov, I. N; Bourne, P. E. (2000). The Protein Data Bank, Nucl Acid Res, 28: 235-242.
Wang, Y; Xiao, J; Suzek, T. O; Zhang, J; Wang, J; Zhou, Z. (2012). PubChem's BioAssay Database, Nucl Acid Res, 40: D400-412.
Seal, A; Aykkal, R; Babu, R. O; Ghosh, M. (2011). Docking study of HIV-1 reverse transcriptase with phytochemicals, Bioinformation, 5: 430-439.
Sharmila, R; Subburathinam, K. M; Aishwarya, S; Margret, A. A. (2013). In silico analysis of andrographolide against cancer, Int J Pharm Sci Drug Res, 5 (2): 56-61.
Jalili, A; Wagner, C; Pashenkov, M; Pathria, G; Mertz, K. D; Widlund, H. R; Lupien, M; Brunet, J. P; Golub, T. R; Stingl, G; Fisher, D. E; Ramaswamy, S; Wagner, S. N. (2012). Dual suppression of the cyclin dependent kinase inhibitors CDKN2C and CDKN1A in human melanoma, J Natl Cancer Inst, 104: 1673-1679.
Machin, P; Catasus, L; Pons, C; Munoz, J; Matias-Guium, X; Prat, J. (2002). CTNNB1 mutations and beta-catenin expression in endometrial carcinomas, Hum Pathol, 33: 206-212.
Stoscheck, C. M; King, L. E. Jr. (1986). Role of epidermal growth factor in carcinogenesis, Cancer Res 46: 1030-1037.
Mendelsohn, J; Baselga, J. (2006). Epidermal growth factor receptor targeting in cancer, Semin Oncol 33: 369-385.
Greten, F. R; Wagner, M; Weber, C. K; Zechner, U; Adler, G; Schmid, R. M. (2001). TGF alpha transgenic mice. A model of pancreatic cancer development, Pancreatology, 1: 363-368.
Hewish, M; Chau, I; Cunningham, D. (2009). Insulin-like growth factor 1 receptor targeted therapeutics: novel compounds and novel treatment strategies for cancer medicine, Recent Pat Anticancer Drug Discov, 4: 54-72.
Sauter, G; Moch, H; Moore, D; Carroll, P; Ker-schmann, R; Chew, K; Mihatsch, M. J; Gudat, F; Waldman, F. (1993). Heterogeneity of erbB-2 gene amplification in bladder cancer, Cancer Res 53 (10): 2199-2203.
Cicenas, J. (2008). The potential role of Akt phosphorylation in human cancers, Int J Biol Markers, 23: 1-9.
Byron, S. A; Pollock, P. M. (2009). FGFR2 as a molecular target in endometrial cancer, Future Oncol, 5: 27-32.
Maekawa, T; Maniwa, Y; Doi, T; Nishio, W; Yoshimura, M; Ohbayashi, C; Hayashi, Y; Okita, Y. (2009). Expression and localization of FOXO1 in non-small cell lung cancer, Oncol Rep, 22: 57-64.
Re, A; Aiello, A; Nanni, S; Grasselli, A; Benvenuti, V; Pantisano, V; Strigari, L; Colussi, C; Ciccone, S; Mazzetti, A. P; Piercontim F; Pinto, F; Bassi, P; Gallucci, M; Sentinelli, S; Trimarchi, F; Bacchetti, S; Pontecorvi, A; Lo Bello, M; Farsetti, A. (2011). Silencing of GST-PI, a prostate cancer prognostic gene, by the estrogen receptor-β and endothelial nitric oxide synthase complex, Mol Endocrinol, 25: 2003-2016.
Heidegger, I; Pircher, A; Klocker, H; Massoner, P. (2011). Targeting the insulin-like growth factor network in cancer therapy, Cancer Biol Ther, 11: 701-707.
Heinlein, C. A; Chang, C. (2004). Androgen receptor in prostate cancer, Endocr Rev, 25: 276-308.
Chene, P. (2003). Inhibiting the p53-MDM2 interaction: An important target for cancer therapy, Nat Rev Caner, 3: 102-109.
Curran, J. E; Weinstein, S. R; Griffiths, L. R. (2002). Polymorphic variants of NFKB1 and its inhibitory protein NFKBIA, and their involvement in sporadic breast cancer, Cancer Lett 188: 103-107.
Liu, Z; Liu, L; Li, M; Wang, Z; Feng, L; Zhang, Q; Cheng, S; Lu, S. (2011). Epidermal growth factor receptor mutation in gastric cancer, Pathology 43: 234-238.
Chinnam, M; Goodrich, D. W. (2011). RB1, development, and cancer, Curr Top Dev Biol, 94: 129-169.
Takano, Y; Takenaka, H; Kato, Y; Masuda, M; Mikami, T; Saegusam, M; Okayasum, I. (1999). Cyclin D1 overexpression in invasive breast cancers: Correlation with cyclin-dependent kinase 4 and oestrogen receptor over expression and lack of correlation with mitotic activity, J Cancer Res Clin Oncol, 125: 505-512.
Hockenbery, D. M. (1994). BCl-2 in cancer, development and apoptosis, J Cell Sci Suppl 18: 51-55.
Wang, J. C. (2002). Cellular roles of DNA topoisomerases: a molecular perspective, Nature Rev 3: 430-438.
Watt, P. M; Hickson, I. D. (1994). Structure and function of type II DNA topoisomerases, Biochemical J 303: 681-695.
Lynch, B. J; Donald, G; Guinee, Jr; Holden, J. A. (1997). Human DNA topoisomerase IIα: A new marker of cell proliferation in invasive breast cancer, Human Pathology 28 (10): 1180-1188.
Depowski, P. L; Rosenthal, S. I; Brien, T. P; Stylos, S; Johnson, R. L; Ross, J. S. (2000). Topoisomerase II α expression in breast cancer. correlation with outcome variables, Modern Pathology, 13 (5): 542–547.
Drwal, M. N; Agama, K; Wakelin, L. P. G; Pommier, Y; Griffith, R. (2001). Exploring DNA Topoisomerase I Ligand Space in Search of Novel Anticancer Agents. PLoS One 2011; 6 (9): e25150.
Champoux JJ. DNA topoisomerases: structure, function, and mechanism, Annu Rev Biochem, 70: 369-413.
Nobili, S; Lippi, D; Witort, E; Donnini, M; Bausi, L; Mini, E; Capaccioli, S. (2009). Natural compounds for cancer treatment and prevention, Pharm Res, 59: 365-378.
Ewesuedo, R. B; Ratain, M. J. (1997). Topoisomerase I inhibitors, The Oncol, 6: 359-364.
Porter, A. G; Janicke, R. V. (1999). Emerging roles of caspases in apoptosis, Cell Death and Differentiation, 6 (2): 99-104.
Mcllwain, D. R; Berfest, G; Mak, T. W. (2013). Caspase functions in cell death and diseases, Cold Spring Harbor Perspective in Biology, 1-29.
Mosmann, T. (1983). Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays, J Immunol Methods, 65: 55-63.
Adinarayana, K. P. S; Babu, P. A; Palakeerthi, S. K. (2012). In silico lead identification by virtual screening and in vitro anti-cancer activities by MTT assay, Inter J Comp Bioinf In Silico Model, 1 (5): 55-57.