fucoxanthin and Urinary-Bladder-Neoplasms

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 μM fucoxanthin inhibited the proliferation of T24 cells in a dose- and time-dependent manner accompanied by the growth arrest at G0/G1 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 μM 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 G0/G1 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.

Topics: Apoptosis; Cell Division; Cell Line, Tumor; Down-Regulation; HSP70 Heat-Shock Proteins; Humans; Proto-Oncogene Proteins p21(ras); Up-Regulation; Urinary Bladder Neoplasms; Xanthophylls

Bladder cancer is a common but serious malignancy. It is widely accepted that chemoprevention may be an effective way to decrease the rate of recurrence and morbidity. We first determined antigrowth and apoptosis-induction activity of fucoxanthin from dietary Laminaria japonica against EJ-1 human bladder cancers. Fucoxanthin significantly reduced the cell viability in a dose- and time-dependent manner. The induction of apoptosis in EJ-1 cells was characterized by morphological changes, DNA ladder, and increased percentage of hypodiploid cells, activating caspase-3 activity. The ratio of apoptotic cells reached >93% after treatment for 72 h with 20 microM fucoxanthin. The findings obtained indicate that fucoxanthin may act as a chemopreventive and/or chemotherapeutic carotenoid in bladder cancer cells by modulating cell viability.

Topics: Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Survival; Chemoprevention; Diet; Flow Cytometry; Humans; Reactive Oxygen Species; Urinary Bladder Neoplasms; Xanthophylls