期刊
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
卷 46, 期 10, 页码 877-884出版社
OXFORD UNIV PRESS
DOI: 10.1093/abbs/gmu080
关键词
fucoxanthin; human bladder cancer T24 cells; G(0); G(1) phase; mortalin; p53
Fucoxanthin, a natural carotenoid, has been reported to have anti-cancer activity in human colon cancer cells, human prostate cancer cells, human leukemia cells, and human epithelial cervical cancer cells. This study was undertaken to evaluate the molecular mechanisms of fucoxanthin against human bladder cancer T24 cell line. MTT analysis results showed that 5 and 10 mu M fucoxanthin inhibited the proliferation of T24 cells in a dose- and time-dependent manner accompanied by the growth arrest at G(0)/G(1) phase of cell cycle, which is mediated by the up-regulation of p21, a cyclin-dependent kinase (CDK)-inhibitory protein and the down-regulation of CDK-2, CDK-4, cyclin D1, and cyclin E. In addition, 20 and 40 mu M fucoxanthin induced apoptosis of T24 cells by the abrogation of mortalin-p53 complex and the reactivation of nuclear mutant-type p53, which also had tumor suppressor function as wild-type p53. All these results demonstrated that the anti-cancer activity of fucoxanthin on T24 cells was associated with cell cycle arrest at G(0)/G(1) phase by up-regulation of p21 at low doses and apoptosis via decrease in the expression level of mortalin, which is a stress regulator and a member of heat shock protein 70, followed by up-regulation of cleaved caspase-3 at high doses.
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