PRELIMINARY STUDY ON SALUBRIOUS EFFECT OF SYRINGIC ACID ON APOPTOSIS IN HUMAN LUNG CARCINOMA A549 CELLS AND INSILICO ANALYSIS THROUGH DOCKING STUDIES
To analyse the anticancer activity of Syringic acid (SA) in lung carcinoma a549 cell line and investigate the mechanism of Bcl-2 inhibition by molecular docking analysis.
The antiproliferative activity of SA was analysed by MTT assay. Apoptosis ratio of SA treated cells was detected by Acridine orange/Ethidium bromide staining. Nuclear morphology of SA treated cells was assessed by propidium iodode staining method. Molecular docking was done with Bcl-2 by Autodock4v4 of human origin and the interaction was studies using pymol.
Preliminary study with MTT assay revealed that SA had cytotoxicity toward A549 lung cancer cells with an IC50 of 30ÂµM. AO/EB staining and PI staining confirms that there is a significant increase in the percentage of apoptotic cells and nuclei respectively of SA treated cells. Further, molecular docking analysis revealed SA inhibited Bcl-2 with a binding score of â€“6.54 Kcal forming three Hydrogen bonds.
These findings suggest that Syringic acid has potential therapeutic benefit and promises to be a weapon against lung cancer.
2. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM.Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893-917.
3. Behera. D. Lung cancer in india. Medicine Update 2012; 22.
4. Woodle ES, Kulkarni S . Programmed cell death. Transplantation 1998; 66:681-691.
5. Korsmeyer SJ. Bcl-2 gene family and the regulation of programmed cell death. Cancer Res 1999; 59:1693s-700s.
6. Reed JC, Bcl-2 and the regulation of programmed cell death, Journal of Cell Biology, 124, 1994,1-6.
7. Chalabi N, Bernard-Gallon DJ, Vasson MP, Bignon YJ. Personalized Med, Medicinal plants as potential sources of lead compounds with anti-platelet and anti-coagulant activities. Mini Rev Med Chem. 2008; 6(6):611-624.
8. Kim D, Jeond S, Lee C. Antioxidant capacity of phenolic phytochemicals from various cultivars of plums. Food Chem., 2003;81: 321-326.
9. Neveu V, Perez-JimÃ©nez J, Vos F, Crespy V, du Chaffaut L, Mennen L et al. Phenol-Explorer: an online comprehensive database on polyphenol contents in foods. Database (Oxford). Epub 2010.
10. Gil, M.I, Ferreres, F, and TomÂ´as-BarberÂ´an,F.A .Effect of modified atmosphere packaging on the flavonoids and vitamin C content of minimally processed swiss chard (beta vulgaris subspecies cycla).Journal of Agricultural and Food Chemistry, 1998; 46:2007â€“2012.
11. Kim,K.H., Tsao, R., Yang,R., and Cui S.W. Phenolic acid profiles and antioxidant activities of wheat bran extracts and the effect of hydrolysis conditions. Food Chemistry.2006; 95:466-473.
12. Beevi SS, Narasu ML, Gowda BB. Polyphenolics profile, antioxidant and radical scavenging activity of leaves and stem of Raphanus sativus L. Plant Foods Hum Nutr. 2010; 65(1):8-17.
13. Jayaram S, Dharmesh SM. Assessment of antioxidant potentials of free and bound phenolics of Hemidesmus indicus (L) R.Br against oxidative damage. Pharmacognosy Res. 2011; 3(4):225-31.
14. Maity N, Nema NK, Abedy MK, Sarkar BK, Mukherjee PK. Exploring Tagetes erecta Linn flower for the elastase, hyaluronidase and MMP-1 inhibitory activity. J Ethnopharmacol.2011; 137(3):1300-5.
15. Hirota A, Taki S, Kawaii S, Yano M, Abe N. 1, 1-Diphenyl-2-picrylhydrazyl radical-scavenging compounds from soybean miso and antiproliferative activity of isoflavones from soybean misotoward the cancer cell lines. Biosci Bio technol Biochem 2000; 64:1038-40.
16. Liu Y, Fang J, Lei T, Wang W, Liu A. Antiendotoxic effect of syringic acid of Radix isatidis. J. Huazhong University. Sci Tech Med Sci 2003; 23:206â€“508.
17. Kampa M, Alexaki VI, Notas G, Nifli AP, Nistikaki A, Hatzoglou Aet al. Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: potential mechanisms of action. Breast Cancer Res. 2004; 6(2):R63-74.
18. Itoh A, Isoda K, Kondoh M, Kawase M, Watari A, Kobayashi M, Tamesada M, Yagi K. Hepatoprotective effect of syringic acid and vanillic acid on CCl4-induced liver injury. Biol Pharm Bull. 2010; 33(6):983-7.
19. Zambonin L, Caliceti C, Vieceli Dalla Sega F, Fiorentini D, Hrelia S, Landi L, Prata C. Dietary phenolic acids act as effective antioxidants in membrane models and in cultured cells, exhibiting proapoptotic effects in leukaemia cells. Oxid Med Cell Longev. 2012:1-12.
20. Gohel A, McCarthy MB, Gronowicz G. Estrogen prevents glucocorticoid-induced apoptosis in osteoblasts in vivo and in vitro.Endocrinology 1999; 140, 5339â€“5347.
21. Chandramohan KVP, Gunasekaran P, Varalakshmi E, Hara Y, Nagini S. In vitro evaluation of the anticancer effect of lactoferrin and tea polyphenol combination on oral carcinoma cells.Cell Biol. Int. 2007; 31, 599â€“608.
22. Morris, G.M., Goodsell, D.S., Halliday, R.S., Huey, R., Hart, W.E., Belew, R.K., and Olson, A.J.Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J. Comp. Chem. 1998; 19 1639â€“1662.
23. Barzi A and Pennell NA. Targeting angiogenesis in non-small cell lung cancer: agents in practice and clinical development. EJCMO 2010. 2(1):31-42.
24. Andreescu, S., Sadik, O.A., McGee, D.W. Effect of natural and synthetic estrogens on a549 lung cancer cells: correlation of chemical structures with cytotoxic effects. Chem. Res. Toxicol. 2005; 18, 466â€“474.
25. Vansteenkiste, J. Improving patient management in metastatic non-small cell lung cancer. Lung Cancer. 2007; 57 (Suppl 2), S12â€“S17.
26. Abaza MS, Al-Attiyah R, Bhardwaj R, Abbadi G, Koyippally M, Afzal M. Syringic acid from Tamarix aucheriana possesses antimitogenic and chemo-sensitizing activities in human colorectal cancer cells. Pharm Biol. 2013; 51(9):1110-24.
27. Siew Hon Ng, Master Thesis. Characterization of Colon Cancer Cell Culture Based Screening Assay to Study Effects of Phenolic Acids. University of Saskatchewan.2011
28. Pitrak, D.L., Tsai, H.C., Mullane, K.M., Sutton, S.H., Stevens, P. Accelerated neutrophil apoptosis in the acquired immunodeficiency syndrome. J. Clin. Invest.1996; 98, 2714â€“2719.
29. Seeliger D, de Groot BL. Ligand docking and binding site analysis with PyMOL and Autodock/Vina. J Comput Aided Mol Des. 2010; 24(5):417-22.
30. Yoshino T, Shiina H, Urakami S, Bcl-2 expression as a predictive marker of hormone-refractory prostate cancer treated with taxane-based chemotherapy. Clinical cancer research, 2006; 12:6116-24.
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.