Cytoprotective Effect of Mangiferin on Benzo(a)pyrene-Induced Lung Carcinogenesis in Swiss Albino Mice
Peramaiyan Rajendran
Department of Medical Biochemistry, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, India
Search for more papers by this authorGanapathy Ekambaram
Department of Medical Biochemistry, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, India
Search for more papers by this authorDhanapal Sakthisekaran
Department of Medical Biochemistry, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, India
Search for more papers by this authorPeramaiyan Rajendran
Department of Medical Biochemistry, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, India
Search for more papers by this authorGanapathy Ekambaram
Department of Medical Biochemistry, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, India
Search for more papers by this authorDhanapal Sakthisekaran
Department of Medical Biochemistry, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, India
Search for more papers by this authorAbstract
Abstract: Antioxidants are one of the key players in tumourigenesis, and several natural and synthetic antioxidants have been shown to have anticancer effects. In the present investigation, the efficacy of mangiferin on the antioxidant status of benzo(a)pyrene-induced lung carcinogenesis in Swiss albino mice was assessed. The animals were divided into five groups. The animals in groups I and V were normal control and mangiferin control, respectively. Groups II, III and IV were administered with benzo(a)pyrene (50 mg/kg body weight, orally) for 4 weeks (twice a week) to induced lung carcinogenesis. Starting 1 week prior to benzo(a)pyrene administration, group III animals were treated with mangiferin (100 mg/kg body weight) in the diet for 18 weeks; 12 weeks after benzo(a)pyrene administration, group III animals were treated with mangiferin that continued until the end of the experiment period (18 weeks). At the end of the experiment period, the reactive oxygen species, glutathione and the activities of antioxidant enzymes were assessed in both lung and liver tissues. The levels of glutathione, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, vitamin E and vitamin C were decreased in group II animals. However, in the mangiferin + benzo(a)pyrene-treated groups III and IV, the levels of GSH and the activities of antioxidant enzymes in both lung and liver were improved when compared with benzo(a)pyrene-induced group II animals. In addition, the finding that mangiferin decreased reactive oxygen species levels and enhanced antioxidant status suggests that this polyphenol might also be of value in the prevention of benzo(a)pyrene-induced lung carcinogenesis.
References
- 1 Georgiou E, Valeri R, Tzimagiorgis G, Anzel J, Krikelis D, Tsilikas C et al . Aberrant p16 promoter methylation among Greek lung cancer patients and smokers: correlation with smoking. Eur J Cancer Prev 2007; 16: 396–402.
- 2
Travis WD,
Travis LB,
Devesa SS.
Lung cancer.
Cancer
1995; 75: 191–202.
10.1002/1097-0142(19950101)75:1+<191::AID-CNCR2820751307>3.0.CO;2-Y CAS PubMed Web of Science® Google Scholar
- 3 Yang J, Lam EWN, Hammad HM, Oberley TD, Oberley LW. Antioxidant enzyme levels in oral squamous cell carcinoma and normal human oral epithelium. J Oral Pathol Med 2002; 31: 71–7.
- 4 Mantovani G, Maccio A, Madeddu C, Mura L, Gramignano G, Lusso MR. Quantitative evaluation of oxidative stress, chronic inflammatory indices and leptin in cancer patients: correlation with stage and performance status. Int J Cancer 2002; 98: 84–91.
- 5 Bakan N, Taysi S, Yilmaz O, Bakan E, Kuşkay S, Uzun N et al . Glutathione peroxidase, glutathione reductase, Cu-Zn superoxide dismutase activities, glutathione, nitric oxide, and malondialdehyde concentrations in serum of patients with chronic lymphocytic leukaemia. Clin Chem Acta 2003; 338: 143–9.
- 6 Mantovani G, Maccio A, Lai P, Massa E, Ghiani M, Santona MC. Cytokine activity in cancer-related anorexia/cachexia: role of megestrol acetate and medroxyprogesterone acetate. Semin Oncol 1998; 25: 45–52.
- 7 Gul M, Kutay FZ, Temocin S, Hanninen O. Cellular and clinical implications of glutathione. Indian J Exp Biol 2000; 38: 625–34.
- 8 Taysi S, Polat F, Gul M, Sari RA, Bakan E. Lipid peroxidation, some extracellular antioxidants, and antioxidant enzymes in serum of patients with rheumatoid arthritis. Rheumatol Int 2002; 21: 200–4.
- 9 Polat MF, Taysi S, Gul M, Cikman O, Yilmaz I, Bakan E et al . Oxidant/antioxidant status in blood of patients with malignant breast tumor and benign breast disease. Cell Biochem Funct 2002; 20: 327–31.
- 10 Finkel T, Holbrook NJ. Oxidants, oxidative stress and the biology of ageing. Nature 2000; 408: 239–47.
- 11 Hockenhery DM, Oltavai ZN, Korsmeyer SJ. Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell 1993; 75: 241–51.
- 12 Johnson IT, Williamson G, Musk SR. Anticarcinogenic factors in plant foods: a new class of nutrients. Nut Rev 1994; 7: 175–204.
- 13 Dragsted LO, Strube M, Larsen JC. Cancer-protective factors in fruits and vegetables: biochemical and biological background. Pharmacol Toxicol 1993; 72: 116–35.
- 14 Yoshimi N, Matsunaga K, Katayama M, Yamada Y, Kuno T, Qiao Z et al . The inhibitory effects of mangiferin, a naturally occurring glucosylxanthone, in bowel carcinogenesis of male F344 rats. Cancer Lett 2001; 163: 163–70.
- 15 Quisumbing E. Medicinal Plants of the Philippines. Katha Publishing Co & JMC Press, Quezon, Philippines, 1978; 538–41.
- 16 Nunez-Selles AJ, Velez Castro HT, Aguero-Aguero J, Gonzalez-Gonzalez J, Naddeo F, De Simone F et al . Isolation and quantitative analysis of phenolic antioxidants, free sugars, and polyols from mango (Mangifera indica L.) stem bark aqueous decoction used in Cuba as a nutritional supplement. J Agric Food Chem 2002; 50: 762–6.
- 17 Bhattacharya SK, Sanyal AK, Ghosal S. Monoamine oxidase-inhibiting activity of mangiferin isolated from canscora decussata. Naturwissenschaften 1972; 59: 651.
- 18 Guha S, Ghosal S, Chattopadhyay U. Antitumor, immunomodulatory and anti-HIV effect of mangiferin, a naturally occurring glucosylxanthone. Chemotherapy 1996; 42: 443–51.
- 19 Yoosook C, Bunyapraphatsara N, Boonyakiat Y, Kantasuk C. Anti-herpes simplex virus activities of crude water extracts of Thai medicinal plants. Phytomedicine 2000; 6: 411–9.
- 20 Li H, Miyahara T, Tezuka Y, Namba T, Nemoto N, Tonami S et al . The effect of kampo formulae on bone resorption in vitro and in vivo. I. Active constituents of Tsu-kan-gan. Biol Pharm Bull 1998; 21: 1322–6.
- 21 Moreira RR, Carlos IZ, Vilega W. Release of intermediate reactive Hydrogen peroxide by macrophage cells activated by natural products. Biol Pharm Bull 2001; 24: 201–4.
- 22 Sanchez GM, Re L, Giuliani A, Nuońez-Selles AJ, Davison GP, Leon-Fernandez OS. Protective effects of Mangifera indica L. extract, mangiferin and selected antioxidants against TPA-induced biomolecules oxidation and peritoneal macrophage activation in mice. Pharmacol Res 2000; 42: 565–73.
- 23 Leiro JM, A lvarez E, Arranz JA, Siso IG, Orallo F. In vitro effects of mangiferin on superoxide concentrations and expression of the inducible nitric oxide synthase, tumour necrosis factor-α and transforming growth factor-β genes. Biochem Pharmacol 2003; 65: 1361–71.
- 24 Mustafa M, Hacker AD, Husain MZ, Ospital JJ, Lee SD. Biochemical Effect of Environmental Pollutants in Animal Lungs. Ann Arbor Science, Ann Arbor, MI, 1977; 59–96.
- 25 Johnson D, Lardy H. Isolation of liver and kidney mitochodria. Meth Enzymol 1967; 10: 94–6.
- 26 Rotruck JT, Pope AL, Ganther HE. Selenium: biochemical role as a component of glutathione peroxidase purification and assay. Science 1973; 179: 588–90.
- 27 Marklund S, Marklund G. Involvement of superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 1974; 47: 469–74.
- 28 Sinha AK. Colorimetric assay of catalase. Anal Biochem 1972; 47: 389–94.
- 29 Staal GEJ, Visser J, Veeger C. Purification and properties of glutathione reductase of human erythrocytes. Biochim Biophys Acta 1969; 185: 39–48.
- 30 Moron MS, DePierre JW, Manerwik KB. Levels of glutathione, glutathione reductase and glutathione-S-transferase activities in rat lung and liver. Biochim Biophys Acta 1979; 582: 67–8.
- 31 Nishikimi M, Appaji N, Yagi K. The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen. Biochem Biophys Res Commun 1972; 46: 849–54.
- 32 Wolf SP. Ferrous ion oxidation in presence of ferric ion indicator xylenol orange for measurement of hydroperoxides. Meth Enzymol 1994; 23: 180–9.
- 33 Gutteridge JM. Thiobarbituric acid-reactivity following iron-dependent free-radical damage to amino acids and carbohydrates. FEBS Lett 1981; 128: 343–6.
- 34 Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193: 265–75.
- 35 Watternberg LW. Chemoprevention of cancer. Cancer Res 1985; 45: 1–8.
- 36 Guner G, Islekel H, Oto O, Hazan E, Acikel U. Evaluation of some antioxidant enzymes in lung carcinoma tissue. Cancer Lett 1996; 103: 233–9.
- 37 Ravid A, Rocker D, Machlenkin A, Rotem C, Hochman A, Kessler-Icekson G et al . 1,25-Dihydroxyvitamin D3 enhances the susceptibility of breast cancer cells to doxorubicin-induced oxidative damage. Cancer Res 1999; 59: 862–7.
- 38 Masotti L, Casali E, Galeotti T. Lipid peroxidation in tumour cells. Free Radic Biol Med 1988; 4: 377–386.
- 39 Sun Y. Free radicals, antioxidant enzymes, and carcinogenesis. Free Radic Biol Med 1990; 8: 583–99.
- 40 Meister A, Anderson ME. Glutathione. Annu Rev Biochem 1983; 52: 711–60.
- 41 Amazzal L, Lapotre A, Quignon F, Bagrel D. Mangiferin protects against 1-methyl-4-phenylpyridinium toxicity mediated by oxidative stress in N2A cells. Neurosci Lett 2007; 418: 159–64.
- 42 Jones GM, Sanford KK, Parshad R, Gantt R, Price FM, Tarone RE. Influence of added catalase on chromosome stability and neoplastic transformation of mouse cells in culture. Br J Cancer 1985; 52: 583–90.
- 43 May JM. Is ascorbic acid an antioxidant for the plasma membrane? FASEB J 1999; 13: 995–1006.
- 44 Langemann H, Torhorst J, Kabiersch A, Krenger W, Honegger CG. Quantitative determination of water- and lipid-soluble antioxidants in neoplastic and non-neoplastic human breast tissue. Int J Cancer 1989; 43: 1169–73.
- 45 Das U. A radical approach to cancer. Med Sci Monit 2002; 8: RA79–92.
- 46 Galati G, Sabzevari O, Wilson JX, O’Brien PJ. Prooxidant activity and cellular effects of the phenoxyl radicals of dietary flavonoids and other polyphenolics. Toxicology 2002; 177: 91–104.