COMPARATIVE STUDY OF IN SILICO AND IN VITRO ANTICANCER ACTIVITY OF TRADITIONAL INDIAN MEDICINAL PLANTS-A REVERSE PHARMACOLOGICAL APPROACH
DOI:
https://doi.org/10.22159/ijcpr.2017v9i4.20761Keywords:
Molegro Virtual docker, MCF-7, HT-29, A549, MTT assayAbstract
Objective: Cancer is one of the major deaths occurring worldwide and its prophylaxis demands the daily consumption of extracts or dietary supplements of traditional medicinal plants which possess anticancer activities. This study focuses on the evaluation of the chemo preventive and antiproliferative effects of the active constituents of Indian medicinal plants such as Withaniasomnifera, Phyllanthusemblica and Zingiberofficinale by in silico and in vitro studies.
Methods: In silico docking analysis is performed using Molegro Virtual Docker choosing the targets as p-glycoprotein and thymidylate synthase for the identified phytoconstituents. In vitro colorimetric cell metabolic activity assay is performed for the standardized extracts of these plants in various cell lines using the standards.
Results: The phytoconstituents in the plants, Withaniasomnifera and Phyllanthusemblica revealed good binding affinity towards thymidylate synthase and p-glycoprotein respectively as compared to that of the standards.
Conclusion: Phyllanthusemblica showed a maximal antiproliferative effect on breast cancer cell lines (MCF-7) when compared to the other plant extracts. Zingiber officinalis was found to inhibit HT-29 cell lines to a greater extent and Withaniasomniferum resulted in highest A549 cell death. A combination of these extracts in any dosage form could be used in the therapeutic efficacy in cancer.
Downloads
References
M Umadevi, KP Sampath Kumar, Debjit Bhowmik, S Duraivel. Traditionally used anticancer herbs in India. J Med Plants Studies 2013;1:56-74.
Michael J Thun, John Oliver De Lancey, Melissa M Center, AhmedinJemal, Elizabeth M Ward. The global burden of cancer: priorities for prevention. Carcinogenesis. 2010;31:100–110.
WHO. World Cancer Report; 2014.
Mahbuba Rahman and Mohammad Rubayet Hasan. Cancer metabolism and drug resistance. Metabolites 2015;5:571–600.
Rose MG, Farrell MP, Schmitz JC. Thymidylate synthase: a critical target for cancer chemotherapy. Clin Colorectal Cancer 2002;1:220-9.
Van Triest B, Pinedo HM, van Hensbergen Y, Smid K, Telleman F, Schoenmakers PS, et al. Thymidylate synthase level as the main predictive parameter for sensitivity to 5-fluorouracil, but not for folate-based thymidylate synthase inhibitors, in 13 nonselected colon cancer cell lines. Clin Cancer Res 1999;5:643-54.
B Yadav, A Bajaj, M Saxena, AK Saxena. In vitro anticancer activity of the root, stem and leaves of Withania somnifera against various human cancer cell lines. Indian J Pharm Sci 2010;72:659–63.
K Takezawa, I Okamoto, S Tsukioka, J Uchida, M Kiniwa, M Fukuoka, et al. Identification of thymidylate synthase as a potential therapeutic target for lung cancer. Br J Cancer 2010;103:354–61.
Bidgoli SA, Azizi E, Zavarhei MD. Association between p53 expression and Bcl-2, P-glycoprotein, topoisomerase II alpha, thymidylate synthase and thymidine phosphorylase as potential therapeutic targets in colorectal cancer patients. Pak J Biol Sci 2007;10:3350-5.
Molegro Virtual Docker User Manual. Available from: http:// www.clcbio.com/wp-content/uploads/2012/09/MVD_Manual.pdf. [Last accessed on 20 Dec 2016]
Susi Kusumaningrum, Emil Budianto, Soleh Kosela, Wahono Sumaryono, FifitJuniarti. The molecular docking of 1,4-naphthoquinone derivatives as inhibitors of Polo-like kinase 1 using molegro virtual docker. J Appl Pharm Sci 2014;4:47-53.
Naeem S, Hylands P, Barlow D. Docking studies of chlorogenic acid against aldose reductase by using molegro virtual docker software. J Appl Pharm Sci 2013;3:13-20.
Thomsen R, Christensen MH. MolDock: a new technique for high-accuracy molecular docking. J Med Chem 2006;49:3315-21.
In silico molecular docking studies and in vitro correlation. Available from: http://shodhganga.inflibnet.ac.in/bitstream/ 10603/66868/14/15.chapter-V. In silico molecular docking studies.pdf. [Last accessed on 20 Dec 2016].
C Vinodhini, K Chitra. Neat synthesis and in silico screening of pyrazole α-amino phosphonates as potent inhibitors of cancer targets. J Chem Pharm Sci 2015;8:584-92.
R-Florence, S Jeeva. In vitro anticancer activity of Gmelinaasiatica l. Leaf against human breast cancer cell line (MCF-7). Int J Pharm Sci Res 2016;7:2116-21.
Tahir Bashir, Mandar Patgaonkar, Selvaa Kumar C, Achhelal Pasi, Kudumula Venkata Rami Reddy. HbAHP-25, an in silico designed peptide, Inhibits HIV-1 Entry by Blocking gp120 Binding to CD4 Receptor. PLoS One 2015;10:e0124839.
KatarÃna Koňariková, Miriam JežoviÄová, Ján KeresteÅ¡, Helena Gbelcová, ZdeňkaÄŽuraÄková, Ingrid Žitňanová. Anticancer effect of black tea extract in human cancer cell lines. Springerplus 2015;4:127.
Vikas Sharma, Shabir Hussain, Moni Gupta, Ajit Kumar Saxena. In vitro anticancer activity of extracts of Mentha Spp. against human cancer cells. Indian J Biochem Biophysics 2014;51:416-9.
N Srivastava, Rumana Ahmad, Mohsin Ali Khan. Evaluation and comparison of the in vitro cytotoxic activity of Withaniasomnifera methanolic and ethanolic extracts against MDA-MB-231 and vero cell lines. Sci Pharm 2016;84:41–59.
VSPK Sankara Aditya J, Naresh Kumar L, Animisha Mokkapati. In vitro anticancer activities of few plant extracts against MCF-7 and HT-29 cell lines. Int J Pharma Sci 2013;3:185-8.