Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Equol Induces Mitochondria-Dependent Apoptosis in Human Gastric Cancer Cells via the Sustained Activation of ERK1/2 Pathway

  • Yang, Zhiping (The First Affiliated Hospital of Xiamen University) ;
  • Zhao, Yan (The First Affiliated Hospital of Xiamen University) ;
  • Yao, Yahong (The First Affiliated Hospital of Xiamen University) ;
  • Li, Jun (The First Affiliated Hospital of Xiamen University) ;
  • Wang, Wangshi (The First Affiliated Hospital of Xiamen University) ;
  • Wu, Xiaonan (Xiamen Medical College)
  • Received : 2016.06.29
  • Accepted : 2016.09.22
  • Published : 2016.10.31
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Abstract

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.

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References

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