Abstract: Although fucoidan has been shown to exert anticancer activity against several types of cancer cell lines, no reports have explored fucoidan-affected cell growth in human urinary bladder cancer cells. In this study, we investigated the anti-proliferative effects of fucoidan in human bladder cancer T24 cells. Our results indicated that fucoidan decreased the viability of T24 cells through the induction of G1 arrest and apoptosis. Fucoidan-induced G1 arrest is associated with the enhanced expression of the Cdk inhibitor p21WAF1/CIP1 and dephosphorylation of the pRB along with enhanced binding of p21 to Cdk4/6 as well as pRB to the transcription factor E2Fs. Further investigations showed the loss of mitochondrial membrane potential and the release of cytochrome c from mitochondria to cytosol, proving mitochondrial dysfunction upon fucoidan treatment with a corresponding increase in the Bax/Bcl-2 expression ratio. Fucoidan-triggered apoptosis was also accompanied by the up-regulation of Fas and truncated Bid as well as the sequential activation of caspase-8. Furthermore, a significant increased activation of caspase-9/-3 was detected in response to fucoidan treatment with the decreased expression of IAPs and degradation of PARP, whereas a pan-caspase inhibitor significantly suppressed apoptosis and rescued the cell viability reduction. In conclusion, these observations suggest that fucoidan attenuates G1-S phase cell cycle progression and serves as an important mediator of crosstalk between caspase-dependent intrinsic and extrinsic apoptotic pathways in T24 cells.
Keywords: fucoidan; bladder cancer; G1 arrest; apoptosis; p21; caspase; tBid
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Park, H.Y.; Kim, G.-Y.; Moon, S.-K.; Kim, W.J.; Yoo, Y.H.; Choi, Y.H. Fucoidan Inhibits the Proliferation of Human Urinary Bladder Cancer T24 Cells by Blocking Cell Cycle Progression and Inducing Apoptosis. Molecules 2014, 19, 5981-5998.
Park HY, Kim G-Y, Moon S-K, Kim WJ, Yoo YH, Choi YH. Fucoidan Inhibits the Proliferation of Human Urinary Bladder Cancer T24 Cells by Blocking Cell Cycle Progression and Inducing Apoptosis. Molecules. 2014; 19(5):5981-5998.
Park, Hye Y.; Kim, Gi-Young; Moon, Sung-Kwon; Kim, Wun J.; Yoo, Young H.; Choi, Yung H. 2014. "Fucoidan Inhibits the Proliferation of Human Urinary Bladder Cancer T24 Cells by Blocking Cell Cycle Progression and Inducing Apoptosis." Molecules 19, no. 5: 5981-5998.