ANTITUMOUR ACTIVITY OF MESO-ZEAXANTHINE AND ITS MECHANISM OF ACTION
Objective: To evaluate the antitumour activity of meso-zeaxanthin and enumerate the mechanism of action.
Methods: In vitro cytotoxicity was determined using transformed cells such as Daltonâ€™s lymphoma ascites tumour cells, Ehrlich ascites tumour cells, L929 cells as well as using normal cells. Tumour reduction was determined by ascites tumour formation and solid tumour reduction. Mechanism of tumour reduction was determined by inhibition of apoptosis as seen by morphology, DNA ladder fraction and induction of P53 and caspase gene and inhibition of BCl2 gene.
Results: Carotenoid meso-zeaxanthin was found to be toxic to Daltonâ€™s Lymphoma ascites cells, Ehrlich ascites tumour cells and L929 cells (IC50, 46, 51 and 37 Î¼g/ml respectively) and was not cytotoxic to normal cells. Meso-zeaxanthin increased the lifespan of animals bearing Ehrlich ascites tumour (69.9%) and decreased the solid tumour induced by Daltonâ€™s Lymphoma ascites tumour. Meso-zeaxanthin was found to induce apoptosis to DLA cells as seen from DNA Lymphoma ascites tumour. Meso-zeaxanthin was found to induce apoptosis to DLA cells as seen from DNA fragmentation, and DNA laddering and up regulation of P  and caspase 3 and 9 down regulation of BCl2 gene expression.
Conclusion: Meso-zeaxanthin which is non-toxic was found to reduce animal tumours.Keywords: Meso-zeaxanthin, Antitumour activity, Apoptosis, P gene-BCl2gene
2. Tanaka T, Shnimizu M, Moriwaki H. Cancer chemoprevention by carotenoids. Molecules 2012;17:3202-42.
3. Thurnham DI. Macular zeaxanthins and lutein: a review of dietary sources and bioavailability and some relationships with macular pigment optical density and age-related macular disease. Nutr Res Rev 2007;20:163â€“79.
4. Xinde Xu, Lihua Zhang, Bin Shao, Xiaoxia Sun, Chi-Tang Ho, Shiming Li. Safety evaluation of meso-zeaxanthin. Food Control 2013;32:678-86.
5. Judy D, Ribaya-Mercado SD, Jeffrey B. Blumberg. Lutein and zeaxanthin and their potential roles in disease prevention. J Am Coll Nutr 2004;23:567â€“87.
6. Ming-Chao Bi, Richard Rosen, Ren-Yuan Zha, Steven A McCormick, E Song, Dan-Ning Hu. Zeaxanthin induces apoptosis in human uveal melanoma cells through bcl-2 family proteins and intrinsic apoptosis pathway. J Evidence-Based Complementary Altern Med 2013;1-12. Doi:10.1155/2013/205082. [Article in Press]
7. Firdous AP, Preethi KC, Kuttan R. Antioxidant potential of meso-zeaxanthin a semi-synthetic carotenoid. Food Chem 2010;119:1096â€“101.
8. Firdous AP, Sindhu ER, Ramnath V, Kuttan R. Antimutagenic and anti-carcinogenic potential of the carotenoid meso-zeaxanthin. Asian Pac J Cancer Prev 2010;11:1345â€“51.
9. Firdous AP, Sindhu ER, Ramnath V, Ramadasan Kuttan. The anti-carcinogenic activity of meso-zeaxanthin in rodents and its possible mechanism of action. Nutr Cancer 2013;65:850â€“6.
10. Firdous AP, Sindhu ER, Ramnath V, Kuttan R. Amelioration of radiation-induced damages in mice by carotenoid meso-zeaxanthin. Int J Radiat Biol 2013;89:171â€“81.
11. Firdous AP, Kuttan R. Amelioration of cisplatin-induced toxicity in mice by carotenoid meso-zeaxanthin. Hum Exp Toxicol 2012;31:710â€“7.
12. Moldeus P, Hogberg J, Orrhenius S, Fleischer SP. In: Methods in enzymology. New York: Academic press; 1978;52:60-71.
13. Boyum A. Isolation of mononuclear cells and granulocytes from human blood. Scand Cand J Clin Invest 1968;21:77â€89.
14. Cole SP. Rapid chemosensitivity testing of human lung tumour cells using MTT assay. Cancer Chem Pharm 1986;17:256-60.
15. Campling BG, Phym J, Barker HM, Cole SP, Lam YM. Chemosensitivity testing of small cell lung cancer using the MTT assay. Br J Cancer 1991;63:75-83.
16. Kuttan R, Bhanumathy P, Nirmala K, George MC. The possible anticancer activity of turmeric. Cancer Lett 1985;29:197-202.
17. Evan G, Littlewood T. A matter of life and cell death. Science 1998;281:1317-22.
18. Flescher E. Jasmonates in cancer therapy. Cancer Lett 2007;245:1â€“10.
19. Ahmed H, Chatterjee BP, Debnath AK. Interaction and in vivo growth inhibition of Ehrlich ascites tumor cells by jacalin. J Biosci 1988;13:419â€“24.
20. Kleinsmith LJ. In: Principles of Cancer Biology. Pearson Benjamin Cummings in San Francisco; 2007. p. 312.
21. Sindhu ER, Firdous AP, Ramnath V, Kuttan R. Effect of carotenoid lutein on N-nitroso diethylamine-induced hepatocellular carcinoma and its mechanism of action. Eur J Cancer Prev 2013;22:320-7.
22. Khan N, Afaq F, Mukhtar H. Apoptosis by dietary factors: the suicide solution for delaying cancer growth. Carcinogenesis 2007;28:233â€“9.
23. Weyhenmeyer B, Murphy AC, Prehn JM, Murphy BM. Tageting the anti-apoptotic BCL-2 family members for the treatment of cancer. Exp Oncol 2012;34:192â€“9.