Study On The Inhibition Effects Of Equol On SKOV-3 Cells Proliferation And Its Molecular Mechanisms

Objective To investigate the effects of equol on the ERK mediated signal transduction pathway and to clarify its mechanisms of proliferation inhibition on human ovarian carcinoma cell line SKOV-3.Methods SKOV-3 cells were treated with different concentration of equol,ranging from 10^-8M to 10^-4M.After the treatment,cell viability, apoptosis rate and cell cycle of each group were examined.Inhibitory effect of equol on SKOV-3 proliferation was tested by MTT method.Cell apoptosis percentage and cell cycle phase distribution were measured by flow cytometric assay(FCM).The expressions of ERK and p-ERK protein were determined using Western blotting.The expression of Bcl-2,Bax and c-myc mRNA were tested by reverse transcription-polymerase chain reaction(RT-PCR).From the mRNA expression level of different genes and protein level,we will understand the underlying mechanism.Results A time- dependent and dose-dependent proliferation inhibition of equol was demonstrated in SKOV-3;the prominent inhibitory concentrations were 50μmol/L and 100μmol/L(P＜0.01) and the 72 hour was the most apparent phase(P＜0.01).The growth inhibition rates of the cancer cells reached 93.92%after being treated with 10^-4M of equol for 72h.Apoptosis rate of SKOV-3 was increased along with the increased of equol concentration.A G2/M cell cycle arrest was induced in SKOV-3 exposed to 50μmol/L equol for 24h.The expression of Bcl-2 and c-myc were decreased at mRNA level in the equol group.The expression of Bax was increased.Western blotting demonstrated that the expressions of p-ERK protein were decreased gradually after being treated with equol for 2h.Conelution Equol could inhibit proliferation and induce apoptosis in ovarian carcinoma cell lines SKOV-3.Its inhibitory effect appears to be due to the down-regulation of p-ERK protein,Bcl-2 and c-myc mRNA,up -regulation of Bax.These results suggest that equol may serve as supplementary therapy and prevent hormone-dependent tumors.