Aqueous extract of Tribulus terrestris Linn induces cell growth arrest and apoptosis by down-regulating NF-κB signaling in liver cancer cells

Ethnopharmacological relevance: A medicinal herb Tribulus terrestris Linn has been used to treat various diseases including hepatocellular carcinoma. The aim of the present study was to investigate the anticancer activity of Tribulus terrestris Linn (TT) in liver cancer cells. Materials and methods: The antitumor activity of aqueous TT extract was analyzed by testing the cytotoxicity and the effect on clonogenecity in HepG2 cells. Apoptosis and cell cycle arrest induced by TT were dissected by flow cytometry and its inhibitory effect on NF-kappa B activity was determined by analyzing the expression levels of NF-kappa B/I kappa B subunit proteins. The suppression of NF-kappa B-regulated gene expression by TT was assessed by RT-PCR. Results: TT extract repressed cloriogenecity and proliferation, induced apoptosis, and enhanced accumulation in the GO/G1 phase of liver cancer cells. It also turned out that TT extract inhibited NE-kappa B-dependent reporter gene expression and NF-kappa B subunit p50 expression, while it enhanced the cellular level of IKB alpha by inhibiting the phosphorylation and degradation of I kappa B alpha. In addition, IKK activity was inhibited in a dose-dependent manner. Furthermore, TT extract suppressed the transcription of genes associated with cell cycle regulation, anti-apoptosis, and invasion. Conclusion: These data showed that TT extract blocks proliferation and induces apoptosis in human liver cancer cells through the inhibition of NF-kappa B signaling. Aqueous TT extract can be used as an anticancer drug for hepatocellular carcinoma patients. (C) 2011 Elsevier Ireland Ltd. All rights reserved.