Fucoidan inhibits the proliferation of human urinary bladder cancer T24 cells by blocking cell cycle progression and inducing apoptosis.

Hye Park,Wun Kim,Gi-Young Kim,Yung Choi,Sung-Kwon Moon,Young Yoo

doi:10.3390/molecules19055981

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.

Highlights

Both cell cycle and apoptosis control mechanisms serve major regulatory functions of growth and development in all living organisms
In this study, we investigated the effects of fucoidan on cell proliferation, cell cycle progression and apoptotic cell death in human urinary bladder carcinoma T24 cell line, and we attempted to clarify the possible signaling pathways involved in fucoidan-induced cell cycle arrest and apoptosis
To examine the molecular mechanisms of G1 arrest in T24 cells treated with fucoidan, we studied the expression of G1 phase regulators using reverse transcription-polymerase chain reaction (RT-PCR) and western blot analyses

Summary

Introduction

Both cell cycle and apoptosis control mechanisms serve major regulatory functions of growth and development in all living organisms. Cell cycle deregulation and apoptosis resulting in uncontrolled cell proliferation are the most frequent alterations that occur during the development and progression of cancer. For this reason, a blockade of the cell cycle and apoptosis induction are regarded as effective strategies for eliminating cancer [1,2]. In mammalian cell cycle regulation, key regulator proteins are cyclin-dependent kinases (Cdks), whose activity is controlled by cyclins and Cdk inhibitors at specific points of the cell cycle [3,4]. The induction of cell cycle arrest associated with apoptotic cell death is one of the strategies for anticancer drug development

Results

Discussion

Conclusion