Anti-proliferation effect on human breast cancer cells via inhibition of pRb phosphorylation by taiwanin E isolated from Eleutherococcus trifoliatus.
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/Cip) and p27(Kip1). The results suggest that taiwanin E inhibits cell cycle progression of MCF-7 at the G0/G1 transition.
Hui-Chun
HC
Wang
Yen-Hsueh
YH
Tseng
Hui-Rong
HR
Wu
Fang-Hua
FH
Chu
Yueh-Hsiung
YH
Kuo
Sheng-Yang
SY
Wang
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D028001:Eleutherococcus / Q000737:chemistry*; D005260:Female; D006131:Growth Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D061986:MCF-7 Cells; D010766:Phosphorylation; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*
D050759:Cyclin-Dependent Kinase Inhibitor p21; D006131:Growth Inhibitors; D010936:Plant Extracts; D016160:Retinoblastoma Protein; D019938:Cyclin D1; D018844:Cyclin-Dependent Kinases