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: 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 activity by fucoidan are mediated via ROS-dependent inactivation of the PI3K/Akt pathway. Drug Dev Res 78 : 37-48, 2017.   © 2016 Wiley Periodicals, Inc.
authors.affiliation: Natural Products Research Team, Marine Biodiversity Institute of Korea, Seocheon, 325-902, Republic of Korea.
authors.forename: Min Ho
authors.initials: MH
authors.lastname: Han
authors.affiliation: Natural Products Research Team, Marine Biodiversity Institute of Korea, Seocheon, 325-902, Republic of Korea.
authors.forename: Dae-Sung
authors.initials: DS
authors.lastname: Lee
authors.affiliation: Anti-Aging Research Center & Blue-Bio Industry RIC, Dongeui University, Busan, 614-714, Republic of Korea.
authors.forename: Jin-Woo
authors.initials: JW
authors.lastname: Jeong
authors.affiliation: Department of Biochemistry, Dongeui University College of Korean Medicine, Busan, 614-052, Republic of Korea.
authors.forename: Su-Hyun
authors.identifier: 0000-0001-9291-5803
authors.initials: SH
authors.lastname: Hong
authors.affiliation: Department of Microbiology, College of Medicine, Inje University, Busan, 608-756, Republic of Korea.
authors.forename: Il-Whan
authors.initials: IW
authors.lastname: Choi
authors.affiliation: Departments of Parasitology and Genetics, College of Medicine, Kosin University, Busan, 602-702, Republic of Korea.
authors.forename: Hee-Jae
authors.initials: HJ
authors.lastname: Cha
authors.affiliation: Department of Chemistry, College of Natural Sciences, Pusan National University, Busan, 609-735, Republic of Korea.
authors.forename: Suhkmann
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan, 609-735, Republic of Korea.
authors.forename: Heui-Soo
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Molecular Biology, College of Natural Sciences and Human Ecology, Dongeui University, Busan, 614-714, Republic of Korea.
authors.forename: Cheol
authors.initials: C
authors.lastname: Park
authors.affiliation: Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju, 690-756, Republic of Korea.
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.affiliation: School of Food Science and Technology, Chung-Ang University, Ansung, 456-756, Republic of Korea.
authors.forename: Sung-Kwon
authors.initials: SK
authors.lastname: Moon
authors.affiliation: Department of Urology, College of Medicine and Institute for Tumor Research, Chungbuk National University, Cheongju, 28644, Republic of Korea.
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: Natural Products Research Team, Marine Biodiversity Institute of Korea, Seocheon, 325-902, Republic of Korea.|Anti-Aging Research Center & Blue-Bio Industry RIC, Dongeui University, Busan, 614-714, Republic of Korea.|Department of Biochemistry, Dongeui University College of Korean Medicine, Busan, 614-052, Republic of Korea.
authors.forename: Yung
authors.initials: Y
authors.lastname: Hyun Choi
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011134:Polysaccharides / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D019098:Telomerase / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
chemical_list: D011134:Polysaccharides; D017382:Reactive Oxygen Species; C007789:fucoidan; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C509186:TERT protein, human; D019098:Telomerase
keywords: ROS; fucoidan; telomerase