Bryostatin-1 inhibits cell proliferation of hepatocarcinoma and induces cell cycle arrest by activation of GSK3beta.

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Wang J, Wang Z, Sun Y, Liu D

Bryostatin-1 inhibits cell proliferation of hepatocarcinoma and induces cell cycle arrest by activation of GSK3beta.

Biochem Biophys Res Commun. 2019 May 7;512(3):473-478. doi: 10.1016/j.bbrc.2019.03.014. Epub 2019 Mar 20.

PubMed ID

30904158 [ View in PubMed

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Abstract

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, 200nM) treatment can suppress cell proliferation and induce G1 cell cycle arrest in PLC/PRF/5 and SMCC7721cell. We also found a significant inhibitory action of bryostatin-1 (100, 200nM) on CyclinD1 activity in PLC/PRF/5cells, and bryostatin-1 can promote ubiquitination-dependent protein degradation of CyclinD1 in PLC/PRF/5cells. Western blot results confirmed that the active form phospho-GSK3beta Tyr216 expression was increased significantly after bryostatin-1 treatment. Activation of GSK3beta 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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Bryostatin 1	G1/S-specific cyclin-D1	Protein	Humans	Unknown	Inhibitor	Details