期刊
BIOTECHNIC & HISTOCHEMISTRY
卷 94, 期 5, 页码 374-380出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/10520295.2019.1574026
关键词
Antiproliferation; beta-catenin; cancer; cell cycle arrest; KHC-4; prostate; roscovitine
资金
- Asia University [ASIA-105-CMUH-01]
- China Medical University Hospital [ASIA-105-CMUH-01]
- Asia University, Taichung, Taiwan [CMU105-ASIA-15]
- China Medical University, Taichung, Taiwan [CMU105-ASIA-15]
KHC-4 is a 2-phenyl-4-quinolone analogue that exhibits anticancer activity. Aberrant activation of beta-catenin signaling contributes to prostate cancer development and progression. Therefore, targeting beta-catenin expression could be a useful approach to treating prostate cancer. We found that KHC-4 can inhibit beta-catenin expression and its signaling pathway in DU145 prostate cancer cells. Treatment with KHC-4 decreased total beta-catenin expression and concomitantly decreased beta-catenin levels in both the cytoplasm and nucleus of cells. KHC-4 treatment also inhibited beta-catenin expression and that of its target proteins, PI3K, AKT, GSK3 beta and TBX3. We monitored the stability of beta-catenin with the proteasomal inhibitor, MG132, in DU145 cells and found that MG132 reversed KHC-4-induced proteasomal beta-catenin degradation. We verified CDK1/beta-catenin expression in KHC-4 treated DU145 cells. We found that roscovitine treatment reversed cell proliferation by arresting the cell cycle at the G2/M phase and beta-catenin expression caused by KHC-4 treatment. We suggest that KHC-4 inhibits beta-catenin signaling in DU145 prostate cancer cells.
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