Anti-proliferation Effect on Human Breast Cancer Cells via Inhibition of pRb Phosphorylation by Taiwanin E Isolated from Eleutherococcus trifoliatus

Abstract

Eleutherococcus trifoliatus has been used as a folk medicine since ancient times, especially as refreshing qi medicines. In our current study, taiwanin E, which possesses strong cytotoxicity, was isolated from the branches of E. trifoliatus by using a bioactivity guided fractionation procedure. Taiwanin E presented a potent anti-proliferation activity on the growth of a human breast adenocarcinoma cell line (MCF-7), with an IC₅₀ value for cytotoxicity of 1.47 μM. Cell cycle analysis revealed that the proportion of cells in the G₀/G₁ phase increased in a dose-dependent manner (from 79.4% to 90.2%) after 48 h exposure to taiwanin E at a dosage range from 0.5 to 4μM. After treatment with taiwanin E, phosphorylation of retinoblastoma protein (pRb) in MCF-7 cells was inhibited, accompanied by a decrease in the levels of cyclin D₁, cyclin D₃ and cyclin-dependent kinase 4 (cdk4) and cdk6; in addition, there was an increase in the expression of cyclin-dependent kinase inhibitors p21^WAF-1/Cip1 and p27^Kip1. The results suggest that taiwanin E inhibits cell cycle progression of MCF-7 at the G₀/G₁ transition.