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FK228 blocks cells survival signal pathways and induces apoptosis of prostate cancer DU145 cells
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Abstract:
Objective: To investigate the underlying mechanism of histone deacetylase (HDAC) inhibitor FK228-induced apoptosis of the prostate cancer cell line DU145.Methods: The inhibitory effect of FK228 on DU145 cell growth and its cytotoxicity were determined by MTT assay; cell cycle arrest was detected by flow cytometry assay; morphological change was observed by Giemsa staining; and defined kinase protein levels were determined by Western blot analysis.Results: FK228 obviously inhibited DU145 cells growth, arrested cell cycle at G0/G1 phase, induced cells morphological changes and degraded several kinase proteins, including EGFR, Her2, Raf-1, Src, Cdk4 and IAP member Survivin. The degradation of these kinases blocked Raf-Mek-Erk and PI3K/Akt survival signal pathways, inducing apoptosis. Conclusion: FK228 may induce DU145 cell apoptosis through depletion of multiple kinase proteins and blockade of survival signal pathways of DU145 cells.
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