In vitro antioxidant and antiproliferative potential of medicinal plants used in traditional Indian medicine to treat cancer.

OBJECTIVE: The goal of this study was to evaluate the antioxidant and antiproliferative activities of 10 traditional medicinal plants, Asclepias curassavica, Ophiorrhiza mungos Linn., Cynodon dactylon (L.) Pers, Costus speciosus (J. Koenig.) Smith Costaceae, Achyranthes aspera L., Amaranthus tristis Roxb., Blepharis maderaspatensis L., Merremia emerginata Hall.f., Aegle marmelos Corr., and Tabernaemontana heyneana Wall., used in the traditional Indian system of medicine as a cure for cancer. The present study focuses on the anticancer potential of traditional medicinal plants to induce apoptosis in cancer cell lines. METHODS: Plants were sequentially extracted with hexane, ethyl acetate, and methanol. The extract was concentrated to yield the crude extract, which was tested for antioxidant activity using 1,1-diphenyl-2-picrylhydrazyl, nitric oxide and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assays on four cancer cell lines and a normal cell line. The anticancer potential of cytotoxic extracts was determined by the Annexin-fluorescein isothiocyanate-conjugated assay in human colon adenocarcinoma cell lines (COLO 320 DM). RESULTS: All the tested extracts showed significant antioxidant and antiproliferative activities in a concentration- and time-dependant manner in the following descending order: A. curassavica > C. dactylon > C. speciosus root > A. tristis > M. emarginata > O. mungos > T. Heyneana > B. maderaspatensis > A. marmelos > A. aspera. CONCLUSION: The results of the present study support the need of further studies to isolate potential anticancer drug with cancer cell-specific cytotoxicity. Additionally, the study supports the anticancer property of medicinal plants used in the traditional Indian medicine system and further evaluation of the selected medicinal plants for an effective anticancer drug with minimal side effects.

ß-sitosterol prevents lipid peroxidation and improves antioxidant status and histoarchitecture in rats with 1,2-dimethylhydrazine-induced colon cancer.

Oxidative stress has become widely viewed as an underlying condition in diseases such as ischemia/reperfusion disorders, central nervous system disorders, cardiovascular disease, cancer, diabetes, etc. The role that antioxidants play in the process of carcinogenesis has recently gained considerable attention. ß-Sitosterol, a naturally occurring sterol molecule, is a relatively mild to moderate antioxidant and exerts beneficial effects in vitro by decreasing the level of reactive oxygen species. The present study evaluated the antioxidant potential of ß-sitosterol in 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis. The enzymatic and nonenzymatic antioxidants and lipid peroxides in colonic and hepatic tissues were evaluated. Generation of reactive oxygen species, beyond the body's endogenous antioxidant capacity, causes a severe imbalance of cellular antioxidant defense mechanisms. Elevated levels of liver lipid peroxides by DMH induction were effectively decreased by ß-sitosterol supplementation. ß-Sitosterol also exhibited a protective action against DMH-induced depletion of antioxidants such as catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione S-transferase, and reduced glutathione in colonic and hepatic tissues of experimental animals. Supplementation with ß-sitosterol restored the levels of nonenzymatic antioxidants (vitamin C, vitamin E, and glutathione). Histopathological alterations in DMH-induced animals were restored to near normal in rats treated with ß-sitosterol. Thus, ß-sitosterol by virtue of its antioxidant potential may be used as an effective agent to reduce DMH-induced oxidative stress in Wistar rats and may be an effective chemopreventive drug for colon carcinogenesis.

Protective effect of morin on cardiac mitochondrial function during isoproterenol-induced myocardial infarction in male Wistar rats.

Altered mitochondrial function and free radical-mediated tissue damage have been suggested as an important pathological event in isoproterenol (ISO)-induced cardiotoxicity. This study was undertaken to know the preventive effect of morin on mitochondrial damage in ISO-induced cardiotoxicity in male Wistar rats. Myocardial infarction (MI) in rats was induced by ISO (85 mg/kg) at an interval of 24 hours for 2 days. Morin was given to rats as pre-treatment for 30 days orally using an intragastric tube. ISO-treated rats showed a significant elevation of mitochondrial thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (HP) level and pre-treatment with morin significantly prevented the increase of TBARS and HP level to near normality. The level of enzymic and non-enzymic antioxidants was decreased significantly in ISO-treated rats and pre-treatment with morin significantly increased the levels of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase, and reduced glutathione to normality. The activities of mitochondrial enzymes such as isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase were decreased significantly in ISO-treated myocardial ischemic rats and upon pre-treatment with morin restored these enzymes activity to normality. In addition, the decreased activities of cytochrome-C oxidase and NADH-dehydrogenases were observed in ISO-treated rats and pre-treatment with morin prevented the activities of cytochrome-C oxidase and NADH-dehydrogenase to normality. Pre-treatment with morin favorably restored the biochemical and functional parameters to near normal indicating morin to be a significant protective effect on cardiac mitochondrial function against ISO-induced MI in rats.

Cancer chemopreventive potential of luteolin-7-O-glucoside isolated from Ophiorrhiza mungos Linn.

The anticarcinogenic potential of the phytocompound Luteolin-7-O-Glucoside (LUT7G), isolated from the leaves of Ophiorrhiza mungos Linn, was studied against 4 different cancer cell lines (COLO 320 DM, AGS, MCF-7, and A549) and normal VERO cell line. The ability of LUT7G to induce apoptosis was determined by its antiradical activity, DNA fragmentation, expression of ß-catenin, and chemopreventive efficacy in vivo by administering rats with DMH (20 mg/kg b.w., s.c.) for 4 consecutive wk and supplementing with 3 different doses throughout the experimental period of 16 wk. LUT7G scavenged 80% of DPPH radicals generated in vitro at 1000 µM and suppressed the expression of ß-catenin to 40% at 120 µM concentrations. LUT7G induced apoptosis by scavenging ROS and suppressing the expression of ß-catenin in COLO 320 DM cells and effectively inhibited ACF development in DMH-induced experimental carcinogenesis. Hence LUT7G can be a potent anticancer drug for colon carcinogenesis.

Chemopreventive potential of Epoxy clerodane diterpene from Tinospora cordifolia against diethylnitrosamine-induced hepatocellular carcinoma.

Medicinal plants are a promising source for identification of lead molecules for cancer therapy. In our continuous search to discover bioactive compounds from natural products, we isolated (5R, 10R)-4R, 8R-dihydroxy-2S, 3R:15, 16-diepoxycleroda-13(16), 17, 12S:18,1S-dilactone (ECD), a diterpenoid from Tinospora cordifolia and studied its chemopreventive potential in diethylnitrosamine (DEN) induced hepatocellular carcinoma (HCC) rats. Fifty male Wistar rats were divided into five groups. Group I served as normal control. Group II-IV were given DEN (0.01% in drinking water) for twenty weeks. In addition, Group III (preventive treatment) received ECD (10 mg/kg body weight) throughout the study. Group IV (curative treatment) received ECD (10 mg/kg body weight) for the last 8 weeks. Group V received ECD alone (10 mg/kg body weight) throughout the experimental period. At the end of the experimental period all the animals were sacrificed and analyzed for biochemical end points to assess the effect of ECD treatment in DEN induced HCC. The animals treated with DEN showed a decrease in the activities of antioxidant (SOD, CAT) and detoxification enzymes (GSH, GPx) with increase in the activities of the hepatic markers (SGOT, SGPT, LDH). Treatment of ECD in both preventive and curative DEN induced animals increased the level of antioxidants and detoxification enzymes, and decreased serum transaminase level and hepatic marker enzymes to near normal. Histopathological and nodular incidence also confirmed that ECD remarkably reduced tumor incidence and reversed damaged hepatocytes to normal. Our findings confirm that ECD exhibits preventive effect against chemically induced HCC in rats. ECD can be a potent chemopreventive drug for HCC.

Temporal patterns of lipid peroxidation product formation and antioxidants activity in oral cancer patients.

The aim of this study was to assess the temporal patterns of (the formation of) thiobarbituric acid reactive substances and the activities of antioxidant enzymes in the erythrocytes of ten healthy adult subjects and ten oral cancer patients of comparable age. The levels of thiobarbituric acid reactive substances and the activities of antioxidant enzymes were assayed at 6-hour intervals using colorimetric methods. The Cosinorwin computer software program was used to analyse the characteristics of biochemical rhythms, such as acrophase, amplitude, and mesor (rhythms: acrophase, amplitude, mesor, etc.). There is a phase delay in erythrocyte thiobarbituric acid reactive substance levels and enzymatic antioxidant activities in oral cancer patients as compared to healthy subjects. The desynchronisation of thiobarbituric acid reactive substance production and enzymatic antioxidant rhythms reflected an alteration of circadian clock function in oral cancer patients and may require specific measures for chronotherapy.