ANTI-PROLIFERATIVE AND APOPTOTIC ACTIVITIES OF SYZYGIUM SAMARANGENSE (WAX APPLE) FRUITS EXTRACT AGAINST HUMAN A549 LUNG CANCER CELL LINES
Objective: Medicinal plants have been in use from time immemorial and their utility has been expanding step by step in the present world. The intention of the present study was to check the anti-proliferative and apoptotic activity of Syzygium samarangense fruits methanolic extract against of A549 cell lines.
Methods: The methanol extract at different concentrations were tested against A549 human lung cancer cell lines for cell viability or cytotoxicity by MTT assay and the hallmark of the apoptosis was analyzed by DNA fragmentation method. The morphological changes resulted due to apoptosis were investigated by Propidium Iodide (PI) staining technique.
Results: The results showed that the tested extracts showed strong and decreased cell viability in a concentration-dependent manner. IC50 value represented that the anti-proliferative activity was found with a minimum concentration of 21.86Î¼g/ml. The presence of ladders of DNA fragments in the DNA fragmentation assay indicates a biochemical hallmark of intrinsic apoptotic cell death. Altered cell morphology after treatment with the extract demonstrated that cells experienced apoptosis.
Conclusion: The present findings encourage further for the isolation and identifying, of active components present in S. samarangense fruit pulps to understand the mechanism of action in vivo that can make an allowance for developing chemotherapeutic agent against cancer.
2. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics. CA Cancer J Clin 2007;57:43â€“66.
3. Brayand F, Moller B. Predicting the future burden of cancer. Nat Rev Cancer 2006;6:63â€“74.
4. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69â€“90.
5. Shu LM, Cheung KL, Khor TO, Chen C, Kong AN. Phytochemicals: cancer chemoprevention and suppression of tumor onset and metastasis. Cancer Metastasis Rev 2010;29:483-502.
6. Mousavi SH, Tayarani-Najaran Z, Hersey P. Apoptosis, from signalling pathways to therapeutic tools. Iran J Basic Med Sci 2008;11:121â€“42.
7. WHO. Cancer: fact sheet. Review; 2013.
8. Hemanth Kumar M, Dhiman V, Choudhary R, Chikara A. Anticancer activity of hydroalcoholic extracts from Paris polyphylla rhizomes against human A549 lung cancer cell lines using MTT assay. Int Res J Pharm 2014;5:290-4.
9. Fidler IJ, Kripke ML. Metastasis results from preexisting variant cells within a malignant tumor. Science 1977;197:893-5.
10. Kligerman MM. editor. Cancer Medicine. Hollabnd JF, Frei E. III, Lea & Febiger, Philadelphia; 1973.
11. Philip PA. Experience with docetaxel in the treatment of gastric cancer. Semin Oncol 2005;32:24-38.
12. Chanchal N Raj, Balasubramaniam A. Pharmacogostic and antimicrobial studies of the leaves of Tabernaemontana divaricata R. br. Pharmacol Online 2011;2:1171-7.
13. Manjunatha BK, Vidya SM. Hepatoprotective activity of Vitex trifolia against carbon tetrachloride-induced hepatic damage. Indian J Pharm Sci 2008;70:241â€“5.
14. Joy PP, Thomas J, Mathew S, Skaria BP. Medicinal plants. Kerala, India: Kerala Agricultural University, Aromatic and Medicinal Plants Research Station; 1998.
15. Kviecinski MR, Felipe KB, Schoenfelder T, de Lemos Wiese LP, Rossi MH, GonÃ§alez E, et al. Study of the antitumor potential of Bidens pilosa (Asteraceae) used in Brazilian folk medicine. J Ethnopharmacol 2008;117:69â€“75.
16. Newman DJ, Cragg GM, Snader KM. Natural products as sources of new drugs over the period 1981â€“2002. J Nat Prod 2003;66:1022â€“37.
17. Reed JC, Pellecchia M. Apoptosis-based therapies for hematologic malignancies. Blood 2005;106:408-18.
18. Yan-Wei H, Chun-Yu L, Chong-Min D, Jian, Wen-Qian, W Zhen-Lun G. Induction of apoptosis in human hepatocarcinoma SMMC-7721 cells in vitro by flavonoids from Astragalus complanatus. J Ethnopharmacol 2009;123:293â€“301.
19. Fulda S. Modulation of apoptosis by natural products for cancer therapy. Planta Med 2010;76:1075â€“9.
20. Morton JF, Miami FL. Java Apple. In: Fruits of Warm Climates; 1987. p. 381-2.
21. Janick J, Paull RE. The Encyclopaedia of Fruit & Nuts. CAB International, United Kingdom; 2008. p. 551-4.
22. Evangeline CA, Irene MV, Amsha Y, Iqbal C. Prolyl endopeptidase inhibitors from Syzygium samarangense (Blume). Merr L M. Perry Z Naturforsch C 2004;59:86-92.
23. Nair AGR, Krishnan S, Ravikrishna C, Madhusudanan KP. New and rare flavonol gycosides from leaves of Syzygium samarangense. Fitoterapia 1999;70:148â€“51.
24. Sivasubramanian V, Devaraj SN. Evaluation of in vitro antioxidant activities and antiproliferative activity of green microalgae, Desmococcus olivaceous and Chlorococcum humicola. J Algal Biomass Utilization 2011;2:82â€“93.
25. Mossman T. Rapid colorimetric assay for cellular growth and survivalâ€“application to proliferation and cytotoxicity assays. J Immunol Methods 1983;65:55-63.
26. Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol 2007;35:495-516.
27. Heng BC, Vinoth KJ, Lu K, Deng X, Ge Z, Bay BH, et al. Prolonged exposure of human embryonic stem cells to heat shock induces necrotic cell death. Biocell 2007;31:405-10.
28. Sarker KP, Obara S, Nakata M, Kitajima I, Maruyama I. Anandamide induces apoptosis of PC-2 cells: involvement of superoxide and caspases-3. FEBS Lett 2000;472:39-44.
29. Surh YJ. Cancer prevention with dietary phytochemicals. Nat Rev Cancer 2003;3:768-80.
30. Kim D, Jeond S, Lee C. Antioxidant capacity of phenolic phytochemicals from various cultivars of plums. Food Chem 2003;81:321-6.
31. Ramos S. Cancer chemoprevention and chemotherapy: dietary polyphenols and signalling pathways. Mol Nutr Food Res 2008;52:507-26.
32. Pan MH, Ho CT. Chemopreventive effects of natural dietary compounds on cancer development. Chem Soc Rev 2008;37:2558-74.
33. Wattenberg LW. Inhibition of carcinogenesis by minor dietary constituents. Cancer Res 1992;52:2085â€“91.
34. Makita H, Tanaka T, Hara A. Chemoprevention of 4-nitroquinoline 1-oxide-induced rat oral carcinogenesis by the dietary flavonoids chalcone, 2-hydroxychalcone, and quercetin. Cancer Res 1996;56:4904â€“9.
35. Thampi N, Shalini V. Bio-Prospecting the in-vitro antioxidant and anti-cancer activities of silver nanoparticles synthesized from the leaves of Syzygium Samarangense. Int J Pharm Pharm Sci 2015;7:269-74.
36. Hui L, Cheng-Yong Q, Guo-Qing H, Hong-Wei X, Mei M, Zhen Y. Mechanism of apoptotic effects induced selectively by ursodeoxycholic acid on human hepatoma cell lines. World J Gastroenterol 2007;3:1652-8.
37. Frederick LK, Xinbo Z. Apoptosis: biochemical aspects and clinical implications. Clin Chim Acta 2002;326:27-45.
38. Cohen GM, Sun XM, Snowden RT, Dinsdale D, Skilleter DN. Key morphological features of apoptosis may occur in the absence of internucleosomal DNA fragmentation. Biochem J 1992;286:331-4.
39. Darling JL. Neuronal and glial tumours in vitro: An overview, In: Doyle A, Griffiths JB, editors. Cell and tissue culture for medical research. John Wiley and Sons Ltd, London; 2000. p. 306-20.
40. Rahman SNSA, Wahab NA, Malek SNA. In vitro morphological assessment of apoptosis induced by antiproliferative constituents from the rhizomes of Curcuma zedoaria. Evidence-Based Complementary Altern Med 2013. doi.org/10.1155/2013/257108. [Article in Press]
41. Karsan A, Harlan JM. Modulation of endothelial cell apoptosis: mechanisms and pathophysiological roles. J Atheroscler Thromb 1996;3:75-80.
42. Rowan S, Fisher DE. Mechanism of apoptotic cell death. Leukemia 1997;11:457-65.