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Bryostatin-1 inhibits cell proliferation of hepatocarcinoma and induces cell cycle arrest by activation of GSK3β
- Wang, Jianfeng, Wang, Zhicheng, Sun, Yu, Liu, Dahai
- Biochemical and biophysical research communications 2019 v.512 no.3 pp. 473-478
- Neritina, Western blotting, aquatic organisms, carcinogenesis, cell cycle checkpoints, cell proliferation, hepatoma, in vivo studies, macrolides, mechanism of action, prospective studies, protein degradation, proteolysis, surface plasmon resonance, tau-protein kinase, therapeutics
- Bryostatin-1, a macrolide lactone derived from marine organism Bugula neritina, has been shown to inhibit carcinogenesis in several prospective clinical trials. In the current study, the therapeutic potential of bryostatin-1 in inhibiting proliferation of hepatocarcinoma was evaluated by in vitro and in vivo studies. The mechanisms of action of bryostatin-1 were predicted by in silico assay and further validated by surface plasmon resonance and western blot assay. Our results show that bryostatin-1 (100, 200 nM) treatment can suppress cell proliferation and induce G1 cell cycle arrest in PLC/PRF/5 and SMCC7721 cell. We also found a significant inhibitory action of bryostatin-1 (100, 200 nM) on CyclinD1 activity in PLC/PRF/5 cells, and bryostatin-1 can promote ubiquitination-dependent protein degradation of CyclinD1 in PLC/PRF/5 cells. Western blot results confirmed that the active form phospho-GSK3β Tyr216 expression was increased significantly after bryostatin-1 treatment. Activation of GSK3β might be responsible for bryostatin-1 induced cyclinD1 degradation and cell cycle arrest. Taken together, bryostatin-1 may inhibit HCC cells proliferation by promoting cyclinD1 proteolysis and inducing cell cycle arrest.