Fucoidan Inhibits the Proliferation of Human Urinary Bladder Cancer T24 Cells by Blocking Cell Cycle Progression and Inducing Apoptosisopen access
- Authors
- Park, Hye Young; Kim, Gi-Young; Moon, Sung-Kwon; Kim, Wun Jae; Yoo, Young Hyun; Choi, Yung Hyun
- Issue Date
- May-2014
- Publisher
- MDPI AG
- Keywords
- fucoidan; bladder cancer; G1 arrest; apoptosis; p21; caspase; tBid
- Citation
- MOLECULES, v.19, no.5, pp 5981 - 5998
- Pages
- 18
- Journal Title
- MOLECULES
- Volume
- 19
- Number
- 5
- Start Page
- 5981
- End Page
- 5998
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/12294
- DOI
- 10.3390/molecules19055981
- ISSN
- 1420-3049
- 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.
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