Equol Induces Mitochondria-Dependent Apoptosis in Human Gastric Cancer Cells via the Sustained Activation of ERK1/2 Pathway.
The cancer chemo-preventive effects of equol have been demonstrated for a wide variety of experimental tumours. In a previous study, we found that equol inhibited proliferation and induced apoptotic death of human gastric cancer MGC-803 cells. However, the mechanisms underlying equol-mediated apoptosis have not been well understood. In the present study, the dual AO (acridine orange)/EB (ethidium bromide) fluorescent assay, the comet assay, MTS, western blotting and flow cytometric assays were performed to further investigate the pro-apoptotic effect of equol and its associated mechanisms in MGC-803 cells. The results demonstrated that equol induced an apoptotic nuclear morphology revealed by AO/EB staining, the presence of a comet tail, the cleavage of caspase-3 and PARP and the depletion of cIAP1, indicating its pro-apoptotic effect. In addition, equol-induced apoptosis involves the mitochondria-dependent cell-death pathway, evidenced by the depolarization of the mitochondrial membrane potential, the cleavage of caspase-9 and the depletion of Bcl-xL and full-length Bid. Moreover, treating MGC-803 cells with equol induced the sustained activation of extracellular signal-regulated kinase (ERK), and inhibiting ERK by U0126, a MEK/ERK pathway inhibitor, significantly attenuated the equol-induced cell apoptosis. These results suggest that equol induces mitochondria-dependent apoptosis in human gastric cancer MGC-803 cells via the sustained activation of the ERK1/2 pathway. Therefore, equol may be a novel candidate for the chemoprevention and therapy of gastric cancer.
The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003 P.R. China.
Zhiping
Z
Yang
The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003 P.R. China.
Yan
Y
Zhao
The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003 P.R. China.
Yahong
Y
Yao
The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003 P.R. China.
Jun
J
Li
The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003 P.R. China.
Wangshi
W
Wang
Xiamen Medical College, Xiamen, Fujian 350108, P.R. China.
Xiaonan
X
Wu
D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D060754:Equol / Q000494:pharmacology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D048789:Phytoestrogens / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology
D048789:Phytoestrogens; D060754:Equol
ERK signalling pathway; equol; gastric cancer; mitochondria-dependent apoptosis