IN VITRO ANTIOXIDANT AND ANTIMUTAGENIC ACTIVITY OF CURCUMIN AGAINST POTENT CHEMOTHERAPEUTIC AGENT DOXORUBICIN
Keywords:
curcumin, micronucleus assay, doxorubicin, antioxidant property, DPPH method, peripheral leukocyteAbstract
The chemopreventive activity of several plants derived materials have been well studied in the recent years. Among them, Curcumin, the mostly investigated dietary phyto constituents have been shown the protective effect in cardiac, renal and hepatic toxicity induced by doxorubicin in human. The protective activity of any phytochemicals mainly depends on their antioxidant property. Thus, the present study was conducted to examine the antioxidant property of laboratory extracted and pure commercial curcumin and antimutagenic action of extracted and pure curcumin against the doxorubicin induced mutagenesis in human leukocyte. To analyze the mutagenicity, parameter like micronucleus assay was conducted in peripheral human leukocytes and to evaluate the antioxidant property, parameter like DPPH free radical scavenging activity was performed. The study results demonstrated that, both the extracted and pure form of curcumin (20µg/ml) induces micronucleus in human leukocytes in an insignificant manner when compared with negative control. Doxorubicin induces significant amount of micronucleus at two variable concentrations (0.50µg/ml and 0.25µg/ml). The micronucleus induction was reduced in human leukocytes pretreated by curcumin for 48 hours in both the concentrations of doxorubucin. Pure as well as extracted Curcumin has been shown strong free radical scavenging activity in a similar pattern as concentration dependant manner. The study reveals that curcumin has antimutagenic potential against chemotherapeutic agent like doxorubicin induced micronucleus in human leukocytes. In addition, it showed strong free radical scavenging activity by DPPH method by both extracted and pure form.
References
Aggarwal, B.B., Shishodia, S. (2006): Molecular targets of dietary agents for prevention and therapy of cancer. – Biochemical Pharmacology 71(10): 1397-1421.
Ak, T., Gülçin, I. (2008): Antioxidant and radical scavenging properties of curcumin. – Chemico-Biological Interactions 174(1): 27-37.
Arcamone, F., Cassinelli, G., Fantini, G., Grein, A., Orezzi, P., Pol, C., Spalla, C. (2000): Adriamycin, 14‐Hydroxydaunomycin, a new antitumor antibiotic from S. peucetius var. caesius. – Biotechnology and Bioengineering 67(6): 704-713.
Bagchi, A. (2012): Extraction of Curcumin. – IOSR Journal of Environmental Science, Toxicol. Food. Tech. 1(3): 1-16.
Birben, E., Sahiner, U.M., Sackesen, C., Erzurum, S., Kalayci, O. (2012): Oxidative stress and antioxidant defense. – World Allergy Organization Journal 5: 9-19.
Borra, S.K., Gurumurthy, P., Mahendra, J., Jayamathi, K.M., Cherian, C.N., Chand, R. (2013): Antioxidant and free radical scavenging activity of curcumin determined by using different in vitro and ex vivo models. – Journal of Medicinal Plants Research 7(36): 2680-2690.
Brand-Williams, W., Cuvelier, M.E., Berset, C.L.W.T. (1995): Use of a free radical method to evaluate antioxidant activity. – LWT-Food science and Technology 28(1): 25-30.
Chen, M., Du, Z.Y., Zheng, X., Li, D.L., Zhou, R.P., Zhang, K. (2018): Use of curcumin in diagnosis, prevention, and treatment of Alzheimer's disease. – Neural Regeneration Research 13(4): 742-752.
De, P., Mukhopadhyay, M. (2019): In vitro anticlastogenic and antioxidant properties of extracted and pure form of curcumin against mitomycin C in human peripheral leukocytes. – Journal of Advanced Pharmacy Research 3(3): 110-116.
Denard, B., Lee, C., Ye, J. (2012): Doxorubicin blocks proliferation of cancer cells through proteolytic activation of CREB3L1. – Elife 14p.
Denard, B., Seemann, J., Chen, Q., Gay, A., Huang, H., Chen, Y., Ye, J. (2011): The membrane-bound transcription factor CREB3L1 is activated in response to virus infection to inhibit proliferation of virus-infected cells. – Cell Host & Microbe 10(1): 65-74.
Dhawan, A., Kayani, M.A., Parry, J.M., Parry, E., Anderson, D. (2003): Aneugenic and clastogenic effects of doxorubicin in human lymphocytes. – Mutagenesis 18(6): 487-490.
Doroshow, J.H. (1986): Role of hydrogen peroxide and hydroxyl radical formation in the killing of Ehrlich tumor cells by anticancer quinones. – Proceedings of the National Academy of Sciences 83(12): 4514-4518.
Duke, J. (2007): Turmeric-The Genus Curcuma. Medicinal and Aromatic Plants-Industrial Profiles Volume 45. – Economic Botany 61(4): 397-398.
Fenech, M., Chang, W.P., Kirsch-Volders, M., Holland, N., Bonassi, S., Zeiger, E. (2003): HUMN project: detailed description of the scoring criteria for the cytokinesis-block micronucleus assay using isolated human lymphocyte cultures. – Mutation Research/Genetic Toxicology and Environmental Mutagenesis 534(1-2): 65-75.
Fogli, S., Nieri, P., CRISTINA BRESCHI, M. (2004): The role of nitric oxide in anthracycline toxicity and prospects for pharmacologic prevention of cardiac damage. – The FASEB Journal 18(6): 664-675.
Gewirtz, D. (1999): A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. – Biochemical Pharmacology 57(7): 727-741.
Goel, A., Kunnumakkara, A.B., Aggarwal, B.B. (2008): Curcumin as “Curecumin”: from kitchen to clinic. – Biochemical Pharmacology 75(4): 787-809.
Gupta, S.C., Kismali, G., Aggarwal, B.B. (2013): Curcumin, a component of turmeric: from farm to pharmacy. – Biofactors 39(1): 2-13.
Hewlings, S.J., Kalman, D.S. (2017): Curcumin: A review of its effects on human health. – Foods 6(10): 11p.
Kocaadam, B., Şanlier, N. (2017): Curcumin, an active component of turmeric (Curcuma longa), and its effects on health. – Critical Reviews in Food Science and Nutrition 57(13): 2889-2895.
Kotwal, G.J., Lahiri, D.K. (Eds.) (2005): Natural products and molecular therapy (Vol. 1056). – New York Academy of Sciences 1056: 520p.
Kunnumakkara, A.B., Anand, P., Aggarwal, B.B. (2008): Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. – Cancer Letters 269(2): 199-225.
Lao, C.D., Ruffin, M.T., Normolle, D., Heath, D.D., Murray, S.I., Bailey, J.M., Boggs, M.E., Crowell, J., Rock, C.L., Brenner, D.E. (2006): Dose escalation of a curcuminoid formulation. – BMC Complementary and Alternative Medicine 6(1): 1-4.
Liu, Z., Huang, P., Law, S., Tian, H., Leung, W., Xu, C. (2018): Preventive effect of curcumin against chemotherapy-induced side-effects. – Frontiers in Pharmacology 9: 9p.
Mensor, L.L., Menezes, F.S., Leitão, G.G., Reis, A.S., Santos, T.C.D., Coube, C.S., Leitão, S.G. (2001): Screening of Brazilian plant extracts for antioxidant activity by the use of DPPH free radical method. – Phytotherapy Research 15(2): 127-130.
Minissi, S., Gustavino, B., Degrassi, F., Tanzarella, C., Rizzoni, M. (1999): Effect of cytochalasin B on the induction of chromosome missegregation by colchicine at low concentrations in human lymphocytes. – Mutagenesis 14(1): 43-49.
Mordente, A., Meucci, E., Silvestrini, A., Martorana, G.E., Giardina, B. (2009): New developments in anthracycline-induced cardiotoxicity. – Current Medicinal Chemistry 16(13): 1656-1672.
Nagabhushan, M., Bhide, S.V. (1986): Nonmutagenicity of curcumin and its antimutagenic action versus chili and capsaicin. – Nutrition and Cancer 8(3): 201-210.
Oakman, C., Moretti, E., Galardi, F., Santarpia, L., Di Leo, A. (2009): The role of topoisomerase IIα and HER-2 in predicting sensitivity to anthracyclines in breast cancer patients. – Cancer Treatment Reviews 35(8): 662-667.
Pawar, H., Karde, M., Mundle, N., Jadav, P., Mehra, K. (2014): Method to prepare pure curcumin. – United State Patent Application 10p.
Pawłowska, J., Tarasiuk, J., Wolf, C.R., Paine, M.J., Borowski, E. (2003): Differential ability of cytostatics from anthraquinone group to generate free radicals in three enzymatic systems: NADH dehydrogenase, NADPH cytochrome P450 reductase, and xanthine oxidase. – Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics 13(5): 245-252.
Ragunathan, I., Panneerselvam, N. (2007): Antimutagenic potential of curcumin on chromosomal aberrations in Allium cepa. – Journal of Zhejiang University Science B 8(7): 470-475.
Rahmani, A.H., Alsahli, M.A., Aly, S.M., Khan, M.A., Aldebasi, Y.H. (2018): Role of curcumin in disease prevention and treatment. – Advanced Biomedical Research 7(1): 9p.
Saleem, M.A., Al-Attar, M.S. (2013): Protective effects of mentha spicata aqueous extract against ifosfamide induced chromosomal aberrations and sperm abnormalities in male albino mice. – ZANCO Journal of Pure and Applied Sciences 28(1): 86-93.
Shafaghati, N., Hedayati, M., Hosseinimehr, S.J. (2014): Protective effects of curcumin against genotoxicity induced by 131-iodine in human cultured lymphocyte cells. – Pharmacognosy Magazine 10(38): 106-110.
Skeel, R.T., Khleif, S.N. (2011): Handbool of cancer chemotheraphy. – Lippincott Williams & Wilkins 875p.
Singh, R.P., Agarwal, R. (2006): Mechanisms of action of novel agents for prostate cancer chemoprevention. – Endocrine-Related Cancer 13(3): 751-778.
Singh, S., Khar, A. (2006): Biological effects of curcumin and its role in cancer chemoprevention and therapy. – Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents) 6(3): 259-270.
Šmerák, P.E.T.R., Polívková, Z., Šestáková, H., Štětina, R., Bárta, I., Langová, M., Turek, B., Bártová, J. (2006). Antimutagenic effect of curcumin and its effect on the immune response in mice. – Czech Journal of Food Science 24(2): 72-83.
Swamy, A.V., Gulliaya, S., Thippeswamy, A., Koti, B.C., Manjula, D.V. (2012): Cardioprotective effect of curcumin against doxorubicin-induced myocardial toxicity in albino rats. – Indian Journal of Pharmacology 44(1): 73-77.
Tewey, K.M., Rowe, T.C., Yang, L., Halligan, B.D., Liu, L.F. (1984): Adriamycin-induced DNA damage mediated by mammalian DNA topoisomerase II. – Science 226(4673): 466-468.
Tobis, J.S., Hochhauser, D. (2014): Cancer and its management. – Wiley-Blackwell 624p.
Thorn, C.F., Oshiro, C., Marsh, S., Hernandez-Boussard, T., McLeod, H., Klein, T.E., Altman, R.B. (2011): Doxorubicin pathways: pharmacodynamics and adverse effects. – Pharmacogenetics and Genomics 21(7): 440-446.
Zoubková, H., Šmerák, P., Polívková, Z. (2015): Antimutagenic Effect of the Ellagic Acid and Curcumin Combinations. – Journal of Environmental & Analytical Toxicology 5(296): 2161-0525.
