Abstract
Fucoidan, a sulfated polysaccharide found in marine algae and brown seaweeds, has been shown to inhibit the in vitro growth of human cancer cells. This study was conducted in cultured human bladder cancer EJ cells to elucidate the possible mechanisms by which fucoidan exerts its anti-proliferative activity, which until now has remained poorly understood. Fucoidan treatment of EJ cells resulted in dose-dependent inhibition of cell growth and induced apoptotic cell death. Flow cytometric analysis revealed that fucoidan led to G1 arrest in cell cycle progression. It was associated with down-regulation of cyclin D1, cyclin E, and cyclin-dependent-kinases (Cdks) in a concentration-dependent manner, without any change in Cdk inhibitors, such as p21 and p27. Furthermore, dephosphorylation of retinoblastoma protein (pRB) by this compound was associated with enhanced binding of pRB with the transcription factors E2F-1 and E2F-4. Overall, our results demonstrate that fucoidan possesses anticancer activity potential against bladder cancer cells by inhibiting pRB phosphorylation.
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Acknowledgments
This work was supported by Blue-Bio Industry Regional Innovation Center (RIC08-06-07) at Dongeui University as a RIC program under Ministry of Trade, Industry & Energy and Busan city and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. NRF-2014R1A2A1A09006983).
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HYP and IWC contributed in running the laboratory work, analysis of the data and drafted the paper. GYK, BWK and WJK contributed to critical reading of the manuscript. WJK and YHC designed the study, supervised the laboratory work and contributed to critical reading of the manuscript. All the authors have read the final manuscript and approved the submission.
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Park, H.Y., Choi, IW., Kim, GY. et al. Fucoidan induces G1 arrest of the cell cycle in EJ human bladder cancer cells through down-regulation of pRB phosphorylation. Rev. Bras. Farmacogn. 25, 246–251 (2015). https://doi.org/10.1016/j.bjp.2015.03.011
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DOI: https://doi.org/10.1016/j.bjp.2015.03.011