Saffron: a potential candidate for a novel anticancer drug against hepatocellular carcinoma

Hepatology. 2011 Sep 2;54(3):857-67. doi: 10.1002/hep.24433. Epub 2011 Jul 19.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Crocus
  • Cyclooxygenase 2 / analysis
  • Diethylnitrosamine
  • Glutathione Transferase / analysis
  • Hep G2 Cells
  • Humans
  • Liver / drug effects
  • Liver Neoplasms, Experimental / pathology
  • Liver Neoplasms, Experimental / prevention & control*
  • Nitric Oxide Synthase Type II / analysis
  • Phytotherapy*
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Rats
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • Antioxidants
  • Plant Extracts
  • Tumor Necrosis Factor-alpha
  • Diethylnitrosamine
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • Glutathione Transferase