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Abstract Title:

Fucoidan Induces ROS-Dependent Apoptosis in 5637 Human Bladder Cancer Cells by Downregulating Telomerase Activity via Inactivation of the PI3K/Akt Signaling Pathway.

Abstract Source:

Drug Dev Res. 2016 Sep 21. Epub 2016 Sep 21. PMID: 27654302

Abstract Author(s):

Min Ho Han, Dae-Sung Lee, Jin-Woo Jeong, Su-Hyun Hong, Il-Whan Choi, Hee-Jae Cha, Suhkmann Kim, Heui-Soo Kim, Cheol Park, Gi-Young Kim, Sung-Kwon Moon, Wun-Jae Kim, Yung Hyun Choi

Article Affiliation:

Min Ho Han

Abstract:

Preclinical Research Fucoidan, a sulfated polysaccharide, is a compound found in various species of seaweed that has anti-viral, anti-bacterial, anti-oxidant, anti-inflammatory, and immunomodulatory activities; however, the underlying relationship between apoptosis and anti-telomerase activity has not been investigated. Here, we report that fucoidan-induced apoptosis in 5637 human bladder cancer cells was associated with an increase in the Bax/Bcl-2 ratio, the dissipation of the mitochondrial membrane potential (MMP,Δψm), and cytosolic release of cytochrome c from the mitochondria. Under the same experimental conditions, fucoidan-treatment decreased hTERT (human telomerase reverse transcriptase) expression and the transcription factors, c-myc and Sp1. This was accompanied by decreased telomerase activity. Fucoidan-treatment also suppressed activation of the PI3K/Akt signaling pathway. Inhibition of PI3K/Akt signaling enhanced fucoidan-induced apoptosis and anti-telomerase activity. Meanwhile, fucoidan treatment increased the generation of intracellular ROS, whereas the over-elimination of ROS by N-acetylcysteine, an anti-oxidant, attenuated fucoidan-induced apoptosis, inhibition of hTERT, c-myc, and Sp1 expression, and reversed fucoidan-induced inactivation of the PI3K/Akt signaling pathway. Collectively, these data indicate that the induction of apoptosis and the inhibition of telomerase activityby fucoidan are mediated via ROS-dependent inactivation of the PI3K/Akt pathway.

Study Type : In Vitro Study

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