Hibiscus-cisplatin combination treatment decreases liver toxicity in rats while increasing toxicity in lung cancer cells via oxidative stress- apoptosis pathway.

Cisplatin (CIS) is a broad-spectrum anti-carcinogen that causes cytotoxic effects both in normal and cancer cells. The purpose of this study was to test whether Hibiscus sabdariffa (HS) extract can reduce CIS-induced hepatotoxicity in rodents and to assess its anticancer activity in vitro. Treatment with HS extract at daily doses of 500 mg/kg before and after a single dose of CIS (10 mg/kg) reduced hepatotoxicity in Wistar male albino rats. HS extract reduced activity of hepatic damage marker enzymes ( i.e. alanine and aspartate aminotransferases), necrosis, and apoptosis in liver tissues of CIS-treated rats. This hepatic protection was associated with reduced oxidative stress in liver tissues. The antioxidant effects of HS were manifested as a normalization of malondialdehyde levels and glutathione levels which were all raised after CIS-induction. In addition, HS treatment resulted in a decrease of catalase, and superoxide dismutase activity. The combined effects of CIS and HS were also studied in two human lung cancer cell lines (A549 and H460). Treatment with HS (20 µg /mL) enhanced the cytotoxic activity of CIS both in A549 and H460 cell lines. Interestingly, HS increased CIS-induced apoptosis and oxidative stress more clearly in A549 cells indicating that HS extract in combination with CIS could increase the efficacy of CIS in the treatment of cancer.

Standardized extract of ginger ameliorates liver cancer by reducing proliferation and inducing apoptosis through inhibition oxidative stress/ inflammation pathway.

Ginger has been proposed as quite a promising candidate for cancer prevention. The purpose of this study was to assess the chemo-preventive effects of ginger. Furthermore, this study investigated the possible mechanisms of a standardized extract drawn from the rhizomes of ginger against diethylnitrosamine (DEN)-induced liver cancer in Wistar rats. The chemo-preventive effects of ginger at doses of 75 mg/kg, 150 mg/kg and 300 mg/kg per day were determined using a liver cancer model which was induced by DEN (Ali et al., 2008) and 2-acetylaminofluorene (2-AAF) in rats. Ginger attenuated carcinogenic changes after 22 weeks of cancer induction by decreasing the quantity and occurrences of hepatic dyschromatic nodules and positive focal areas as well as decreasing the amount of placental glutathione S-transferase (GST) in the livers of DEN/2-AAF-treated rats. Moreover, in rats, ginger counteracts DEN-influenced oxidative stress and decreases myeloperoxidase, malondialdehyde and protein carbonyl concentrations in the liver. This was determined by observing the restoration of superoxide dismutase, catalase, GST and glutathione. Immunohistochemical bleaching in rat livers showed that ginger prevented the increase in cell-positive numbers for Ki-67, cyclooxygenase-2 and nuclear factor kappa B p65. Ginger also inhibited the number of positive cells in DEN/2-AAF-treated rats for TUNEL, M30 and caspase-3 liver tissues. This research shows that ginger has an important chemo-preventative impact on liver cancer by inhibiting the growth of cells and inducing apoptosis. By reducing oxidative and inflammatory damage, ginger protects rat liver against cancer.

Molecular characterization of the grape seeds extract's effect against chemically induced liver cancer: In vivo and in vitro analyses.

The purpose of this study was to investigate the anti-cancer property of grape seed extract (GSE) during early stages of developing liver cancer using a two-stage carcinogenic model combining diethylnitrosamine (DEN) and 2-Acetyl Aminofluorene (2-AAF). Administration of GSE at doses 25, 50 and 100 mg/kg per day started at the beginning of promotion periods and continued for 14 weeks. GSE dramatically inhibited pre-neoplastic foci formation as well as significantly decreased the number and the area of placental glutathione-S-transferase in livers of DEN-2AAF-treated rats by approximately 4 & 10 fold deductions, respectively. GSE's effects were associated with induced apoptosis, reduced cell proliferation, decreased oxidative stress and down regulation of histone deacetylase activity and inflammation makers, such as cyclooxygenase 2, inducible nitric oxide synthase, nuclear factor-kappa B-p65 and p- phosphorylated tumor necrosis factor receptor expressions in liver. GSE treatment also decreased the viability of HepG2 cells and induced early and late apoptosis through activating caspase-3 and Bax. Furthermore, GSE induced G2/M and G1/S cell cycle arrest. The present study provides evidence that the GSE's anticancer effect is mediated through the inhibition of cell proliferation, induction of apoptosis, modulating oxidative damage and suppressing inflammatory response.