Apoptosis and Antioxidant Activities of Catharanthus rosues [L] G.Don Extract on Breast Cancer Cell Line

Wahyu Widowati, Tjandrawati Mozef, Chandra Risdian, Hana Ratnawati, Susi Tjahyani, Ferry Sandra

Abstract


Tapak dara or Madagascar Periwinkle (Catharanthus roseus [L] G.Don), a natural plant, is empirically reported to have promising anticancer activity. To elucidate its mechanism, a research was conducted to investigate the possible ethanol extract of  C. roseus in inducing apoptosis on breast cancer cell line (T47D). Antioxidant activity of C. roseus was investigated as well. Sub-G1 flowcytometric apoptotic analysis result showed that extract of C. roseus at 6.25 μg/mL induced apoptosis for 26.365%. Increasing extract concentration resulted an increasing apoptotic level as well, extract at concentration of 12.5 μg/mL induced apoptosis for 22.235%.  Meanwhile doxorubicin at concentration of 10 μg/mL induced apoptosis for 36.055%. The antioxidant activity was determined by using in vitro assay: inhibition of  2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity. Antioxidant activity of C. roseus extract were compared to quercetin and butylated hydroxyanisol (BHA), as positive controls.  The results showed that DPPH IC50 of C. roseus extract, quercetin and BHA were 358.411 μg/mL, 19.200 μg/mL  and  94.178 μg/mL, respectively. We suggest that C. roseus extract had a potential anticancer activity by inducing apoptosis.

Key words : antioxidant, DPPH, Catharanthus roseus, apoptosis, breast cancer, T47D


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References


Abdolmohammadi, M.H., S. Fouladdel, A. Shafiee, G. Amin, S.M. Ghaffari, and E. Azizi. 2008. Anticancer effects and cell cycle analysis on human breast cancer T47D cells treated with extracts of Astrodaucus persicus (Boiss.) Drude in comparison to doxorubicin. DARU. 16 (2):112-118.

Abdolmohammadi, M.H., S. Fouladdel, A. Shafiee, G. Amin, S.M. Ghaffari, and E. Azizi. 2009. Antiproliferative and apoptotic effect of Astrodaucus orientalis (L.) drude on T47D human breast cancer cell line: Potential mechanisms of action. African Journal of Biotechnology. 8 (17): 4265-4276.

Ahmad, N.H., R.A Rahim, and I. Mat. 2010. Catharanthus roseus aqueous extract is cytotoxic to Jurkat leukaemic T-cells but induces the proliferation of normal peripheral blood mononuclear cells. Tropical Life Sciences Research. 21(2):105–11.

Caron, J.M., and M. Herwood. 2007. Vinblastine, a chemotherapeutic drug, inhibits palmitoylation of tubulin in human leukemic lymphocytes. Chemotherapy. 53(1): 51-58.

Chattopadhyay, R.R., S.K. Sarkar, S. Ganguly, R.N. Banerjee, and T.K. Basu. 1991. Hypoglycemic and antihyperglycemic effects of leaves of Vincarosea Linn. lnd. J. Physiol. Pharmacol. 33:145-15 I.

Chattopadhyay, R..R., R.N. Ba.nerjee, Sarkar, S, Ga.nguly and T.K. Ba.su, 1992. Anti-inflammatory. and acute toxicity studies with leaves of Vinca rosea Linn in experimental animals. Indian J. Physiol. Pharm.acoll. 36: 291-292.

Chen, S, and E. Yan. 2007. Breast Cancer in a Postmenopausal Obese Female Patient. Obesity Management. 3(3): 133-135.

Comin-Anduix, B., N. Agell, O.Bachs, J. Ovadi and M. Cascante. 2001. A New Bis-Indole, KARs, Induces Selective M Arrest with Specific Spindle Aberration in Neuroblastoma Cell Line SH-SY5Y. Moleuclar Pharmacology. 60(6):1235-1242.

Compton, M.M. 1992. A biochemical hallmark of apoptosis: Internucleosomal degradation of the genome. Cancer Metastasis Reviews 11:105-119.

Dobashi, Y.T. Takehana T, and A. Ooi. 2003. Perspectives on cancer therapy: cell cycle blockers and perturbators. Curr Med Chem. 10(23): 2549-58.

Fan, M., M.E. Goodwin, M.J. Birrer, and T.C. Chambers. 2001. The c-Jun NH2-terminal protein kinase/AP-1 pathway is required for efficient apoptosis induced by vinblastine. Cancer Res. 61:4450–4458.

Frum, Y. And A.M. Viljoen. 2006. In vitro 5-Lipoxygenase and Anti-Oxidant Activities of South African Medicinal Plants Commonly Used Topically for Skin Disease. Skin Pharmacol Physiol. 19:329–335.

Ghosh, R.K. and I. Gupta. 1980. Effect of Vinca rosea and Ficus racemososus on hyperglycemia in rats. Indian J. Anim. Health. 19: 145-148.

Gordon, M.H. 2001. Measuring antioxidant activity. In Pokorny J, N. Yanishlieva, M. Gordon. eds. Antioxidant in food. Woodhead Publihing Limited. Cambridge England.

Han, S.S., S.C. Lo, Y.W. Choi, J.H. Kim, and S.H. Baek. 2004, Antioxidant Activity of Crude Extract and Pure Compounds of Acer ginnala Max. Bull. Korean Chem. Soc. 25(3):389-391.

Hanf,V. and U. Gonder. 2005. Nutrition and primary prevention of breast cancer: foods, nutrients and breast cancer risk. Eur. J. Obstet. Gynecol. Reprod. Biol. 123:139-149.

Higuchi, M., T. Honda, R.J. Proske, and E.T.H. Yeh. 1998. Regulation of reactive oxygen species-induced apoptosis and necrosis by caspase 3-like proteases. Oncogene, 17: 2753-2760.

Johnstone, R.W., A.A. Ruefli, and S.W. Lowe. 2002 Apoptosis: A Link between Cancer Genetics and Chemotherapy. Cell. 108(25):153-164.

Kikugawa, K, A. Kunugi, and T. Kurechi, 2001, Chemistry and implications of degradation of phenolic antioxidants. In Hudson, B. J. F, ed. Food Antioxidants. Elsevier Applied Modern Toxicology. Mc. Graw-Hill. Singapore.

Kinghorn, A.D., N.R. Farnsworth, D.D. Soejarto, G.A. Cordell, S.M. Swanson, J.M. Pezzuto, M.C.Wani, M.E. Wall, N.H. Oberlies, J. David, D.J. Keoll, R.A. Kramer, W.C.Rose, G.D.Vite, C.R. Fairchild, R.W. Peterson, and R.Wild. 2003. Novel strategies for the discovery of plant-derived anticancer agents. Pharm. Biol. 41: 53-67.

Kaufmann, S.H. 1989. Induction of endonucleolytic DNA cleavage in human acute myelogenous leukemia cells by etoposide, campotechin and other cytotoxic anticancer drugs: a cautionary note. Cancer Res. 49:5870.

Kaufmann, S.H., and W.C. Earnshaw. Induction of Apoptosis by Cancer Chemotherapy. Experimental Cell Research. 256: 42-49.

Kumaraguruparan, R., R. Subapriya, P. Viswanathan, and S. Nagini. 2002. Tissue lipid peroxidation and antioxidant status in patients with adenocarcinoma of the breast. Clinica Chimica Acta. 325(1-2):165-170.

Lopez, D., and M. Sekharam. 2008. Purified human chorionic gonadotropin induces apoptosis in breast cancer. Mol Cancer Ther. 7(9):2837–44.

Lowe, S.W., and A.W. Lin. 2000. Apoptosis in cancer. Carcinogenesis. 21(3):85-495.

Margolis, R.L., C.T. Rauch, and L. Wilson L. 1980. Mechanism of colchicine-dimer addition to microtubule end: implication for the microtubule polymerization mechanism. Biochemistry, 19:5550–5557

McCloskey, T.W., N. Oyaizu, M. Coronesi and S. Pahwa. 1994. Use a Flow Cytometric Assay to Quantitate Apoptosis in Human Lymphocytes. Clinical Immunology and Immunopathology. 71(1):14-18.

Miliauskas, G., P.R.Venskutonis, and T.A. van Beek. 2003. Screening of radical scavenging activity of some medicinal and aromatic plant extracts. Food Chemistry, Available online 24 October 2003.

Mooney, L.M., K.A. Al-Sakkaf , B.L. Brown, and P.R.M. Dobson . 2002. Apoptotic mechanisms in T47D and MCF-7 human breast cancer cells. British Journal of Cancer. 87:909–917.

Nobili, S., D. Lippi, E. Witort, M. Donnini, L. Bausi, E. Mini, and S. Cappaccioli. 2009. Natural compounds for cancer treatment and prevention. Pharmacological Research. 59:365-378.

Okonogi, S., C. Duangrat, S. Anuchpreeda, S. Tachakittirungrod, and S. Chowwanapoonpohn. 2007. Comparison of antioxidant capacities and cytotoxicities of certain fruit peels. Food Chemistry. 103:839-846.

Ray, G., S. Batra, N.K. Shukla, S. Deo, V. Raina, S. Ashok, and S.A. Husain. 2000. Lipid peroxidation, free radical productionand antioxidant status in breast cancer. Breast Cancer Research and Treatment. 59:163-170.

Ribble, D., N.B. Goldstein, D.A. Norris, and Y.G. Shellman. 2005. A simple technique for quantifying apoptosis in 96-well plates. BMC Biotechnology. 5(12):1-7.

Rischer, H., M. Oresic, B. Seppa¨nen-Laakso, M. Katajamaa, F. Lammertyn, W. Ardiles-Diaz, M.C.E. Van Montagu, D. Inze, K.M. Oksman-Caldentey, and A. Goossens. 2006. Gene-to-metabolite networks for terpenoid indole alkaloid biosynthesis in Catharanthus roseus cells. PNAS. 103(14):5614-5619.

Sapi, J. and G. Massiot. 1994. Heterocylclic Compounds. In : Saxton, J.E. (Ed.). Monoterpenoicls Indole Alkaloids, Part 4. Wiley, Chichester, 523-646.

Sarkar, F.H., and Y.W. Li. 2007. Targeting multiple signal pathways by chemopreventive agents for cancer prevention and therapy. Acta Pharmacol.Sin, 28:1305-1315.

Schwartzman, R.A. and J.A. Cidlowski. 1993. Apoptosis : the biochemistry and molecular biology of programmed cell death. Endo.Rev., 14:133.

Sinha, R.J., R. Singh R, S. Mehrotra, R.K. Singh. 2009. Implications of free radicals and antioxidant levels in carcinoma of the breast: A never-ending battle for survival. Indian Journal of Cancer., 46(2):146-150.

Shkreta L., U. Froehlich, E.R. Paquet, J.Toutant, S.A. Elela, and B. Chabot. 2008. Anticancer drugs affect the alternative splicing of Bcl-x and other human apoptotic genes. Mol Cancer Ther 2008; 7(6):1398–409.

Somani, R., P. Kalantri, V.J. Kadam. 2010. Apoptosis : Concept, mechanism and clinical implications. Latest Reviews. 8(2).

Suffness, M., and J.M. Pezzuto. 1990. Assays related to cancer drug discovery. In: Hostettmann, K. (Ed.), Methods in plant biochemistry: Assays for Bioactivity. Academic Press, London:71–133.

Tan, M.L., S.F. Sulaiman, N. Najimuddin, M.R. Samian, and T.S.T. Muhammad. 2005. Methanolic extract of Pereskia bloe (Kunth) DC. (Cactaceae) induces apoptosis in breast carcinoma, T47D cell line. J. Ethnopharmacol. 96:287-294.

Telford, W.G., L.E. King, P.J. Fraker. 1994. Rapid quantitation of apoptosis in pure and heterogenous cell populations using flow cytometry. Journal of Immunological Methods. 172:1-16.

Ueda J.Y., Y. Tezuka, A.H. Banskota, Q. Le Tran and Q.K. Tran. 2002. Antiproliferative activity of Vietnamese medicinal plants. Biol. Pharm. Bull, 25: 753-760.

Unlu, G.V., F.Candan, A. Sokmen, D. Dafefera, M. Polissiou,E. Sokmen, Donmez, and B. Tepe. 2003. Antimicrobial and antioxidant activity of the essential oil and methanol extracts of Thymus pectinatus Fisch. et Mey. Var. pectinatus (Lamiaceae). J. Agric. Food Chem. 51:63-67.

Valeriote, F., C.K. Grieshaber, J. Media, H. Pietraszkewics, J. Hoffmann, M. Pan, and S. McLaughlin.2002. Discovery and development of anticancer agents from plants. J. Exp. Ther. Oncol. 2: 228-236.

Waxman, D.J. and P.S. Schwartz 2003. Harnessing apoptosis for improved anticancer gene therapy. Cancer Res. 63:8563–72.




DOI: http://dx.doi.org/10.14499/indonesianjcanchemoprev1iss2pp99-107

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