Abstract 1621: Potent anti-cancer effect of crocin against hepatocellular carcinoma: A preclinical study

Abstract Background: This is a follow up of our study published in September issue of Hepatology and featured in October issue of Science News that documented the antic-cancer potential of saffron. Here, we show the chemopreventive actions and mechanisms of saffron-based bioactive ingredient; crocin, against diethylnitrosamine (DEN)-induced liver cancer in rats. Methods: Administration of crocin at two doses of 100 and 200 mg/kg body wt per day was started two weeks prior to the DEN injection and was continued for 22 weeks. Result: Crocin decreased the number and the area of placental glutathione-S-transferase positive foci in livers of DEN-treated rats. Furthermore, crocin 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 crocin inhibited the DEN-mediated elevations in numbers of cells positive for Ki-67, cyclooxygenase 2, inducible nitric oxide synthase, nuclear factor-kappa Bp-65 and the phosphorylated tumor necrosis factor receptor. Crocin also blocked the depletion in the number of cells positive for TUNEL 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 NFkB activation, increased cleavage of caspase-3, as well as DNA damage and cell cycle arrest upon saffron treatment. Conclusion: The present study provides evidence that crocin exerts a significant chemopreventive effect against liver cancer through inhibition of cell proliferation and induction of apoptosis. This report also shows some evidence that crocin protects rat liver from cancer via modulating oxidative damage and suppressing inflammatory response. This study is funded by Emirates Foundation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1621. doi:1538-7445.AM2012-1621