Saffron has been proposed as a promising candidate for cancer chemoprevention. The purpose of this investigation was to investigate the chemopreventive action and the possible mechanisms of saffron against diethylnitrosamine (DEN)-induced liver cancer in rats. Administration of saffron at doses of 75, 150, and 300 mg/kg/day was started 2 weeks prior to the DEN injection and was continued for 22 weeks. Saffron significantly reduced the DEN-induced increase in the number and the incidence of hepatic dyschromatic nodules. Saffron also decreased the number and the area of placental glutathione S -transferase–positive foci in livers of DEN-treated rats. Furthermore, saffron counteracted DEN-induced oxidative stress in rats as assessed by restoration of superoxide dismutase, catalase, and glutathione-S-transferase levels and diminishing of myeloperoxidase activity, malondialdehyde and protein carbonyl formation in liver. The results of immunohistochemical staining of rat liver showed that saffron inhibited the DEN-mediated elevations in numbers of cells positive for Ki-67, cyclooxygenase 2, inducible nitric oxide synthase, nuclear factor-kappa B p-65, and phosphorylated tumor necrosis factor receptor. Saffron also blocked the depletion in the number of cells positive for TUNEL (terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling) and M30 CytoDeath in liver tissues of DEN-treated rats. In vitro experiments carried out using HepG2 cells also confirmed these findings and showed inhibition of nuclear factor-kappa B activation, increased cleavage of caspase-3, as well as DNA damage and cell cycle arrest upon saffron treatment. Conclusion: This study provides evidence that saffron exerts a significant chemopreventive effect against liver cancer through inhibition of cell proliferation and induction of apoptosis. This report also shows some evidence that saffron protects rat liver from cancer via modulating oxidative damage and suppressing inflammatory response. (HEPATOLOGY 2011;)

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.

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