AIM: To investigate the anti-tumor effects of equol in gastric cancer cells and the underlying molecular mechanisms.METHODS: MGC-803 cells were employed for in vitro experiments in this study. Cells were treated with control(vehicle,0.1% DMSO) or equol under specified dose titration or time courses. Cell viability was examined by MTS assay,and the levels of Ki67 were determined by q PCR and immunofluorescent assay. Changes in cell cycle distribution and apoptosis rate were detected by flow cytometry. The m RNA expression of cyclin E1 and P21WAF1 was determined by q PCR. The protein levels of cell cycle regulators,PARP and Caspase-3 cleavage,and the phosphorylation of Akt were examined by Western blot. In addition,to characterize the role of elevated Akt activation in the anti-tumor effect exerted by equol,Ly294002,a PI3K/AKT pathway inhibitor,was used to pretreat MGC-803 cells. RESULTS: Equol(5,10,20,40,or 80 μmol/L) inhibited viability of MGC-803 cells in a dose- and timedependent manner after treatment for 24,36,or 48 h(P < 0.05 for all). Equol also decreased the m RNA(P <0.05 for 12 and 24 h treatment) and protein levels of Ki67. Equol treatment significantly induced G0/G1 cell cycle arrest(P < 0.05),with the percentages of G0/G1 cells of 32.23% ± 3.62%,36.31% ± 0.24%,45.58% ± 2.29%,and 65.10% ± 2.04% for equol(0,10,20,or 30 μmol/L) treatment,respectively,accompanied by a significant decrease of CDK2/4(P < 0.05 for 24 and 48 h treatment) and Cyclin D1/Cyclin E1(P < 0.05),and an increased level of P21WAF1(P < 0.05). A marked increase of apoptosis was observed,with the percentages of apoptotic cells of 5.01% ± 0.91%,14.57% ± 0.99%,37.40% ± 0.58%,and 38.46% ± 2.01% for equol(0,5,10,or 20 μmol/L) treatment,respectively,accompanied by increased levels of cleaved PARP and caspase-3. In addition,we found that equol treatment increased P-Akt(Ser473 and Thr308) at 12 and 24 h compared to vehicle-treated control; longer treatment for 48 h decreased P-Akt(Ser473 and Thr308). P-Akt at Thr450,however,was decreased by equol treatment at all time points examined(P < 0.05 for all). Moreover,Akt inhibition by Ly294002 could not prevent but led to enhanced G0/G1 arrest and apoptosis. CONCLUSION: Equol inhibits MGC-803 cells proliferation by induction of G0/G1 arrest and apoptosis. Its anti-cancer effects are likely mediated by dephosphorylation of Akt at Thr450. AIM: To investigate the anti-tumor effects of equol in gastric cancer cells and the underlying molecular mechanisms. METHODS: MGC-803 cells were employed for in vitro experiments in this study. Cells were treated with control (vehicle, 0.1% DMSO) or Cell viability was examined by MTS assay, and the levels of Ki67 were determined by q PCR and immunofluorescent assay. Changes in cell cycle distribution and apoptosis rate were detected by flow cytometry. The m RNA expression of The protein levels of cell cycle regulators, PARP and Caspase-3 cleavage, and the phosphorylation of Akt were examined by Western blot. In addition, to characterize the role of elevated Akt activation in the anti RESULTS: Inhibitory activity of MGC-803 cells (5,10,20,40, or 80 μmol / L) in a dose- and timedependent ma Equil also decreased the m RNA (P <0.05 for 12 and 24 h treatment) and protein levels of Ki 67. Equol treatment significantly induced G0 / G1 cell (P <0.05 for all) cycle arrest (P <0.05) with the percentages of G0 / G1 cells of 32.23% ± 3.62%, 36.31% ± 0.24%, 45.58% ± 2.29%, and 65.10% ± 2.04% for equol (0, or 30 μmol / L) treatment, respectively, accompanied by a significant decrease of CDK2 / 4 (P <0.05 for 24 and 48 h treatment) and Cyclin D1 / Cyclin E1 <0.05) A marked increase of apoptosis was observed, with the percentages of apoptotic cells of 5.01% ± 0.91%, 14.57% ± 0.99%, 37.40% ± 0.58%, and 38.46% ± 2.01% for equol (0, 10, or 20 μmol / L) treatment, respectively, accompanied by increased levels of cleaved PARP and caspase-3. In addition, we found that equol treatment increased P-Akt (Ser473 and Thr308) at 12 and 24 h compared to vehicle- treated control; longer treatment for 48 h decreased P-Akt (Ser473 and Thr308). P-Akt at Thr450, however, was decreased by equol treatment at all time examined (P <0.05 for all). Moreover, Akt inhibition by Ly294002 could not prevent but led to enhanced G0 / G1 arrest and apoptosis. CONCLUSION: Equol inhibits MGC-803 cells proliferation by induction of G0 / G1 arrest and apoptosis. Its anti-cancer effects are likely mediated by dephosphorylation of Akt at Thr450.