title: Fucoxanthin induces growth arrest and apoptosis in human bladder cancer T24 cells by up-regulation of p21 and down-regulation of mortalin.
abstract: Fucoxanthin, a natural carotenoid, has been reported to have anti-cancer activity in human colon cancer cells, human prostate cancer cells, human leukemia cells, and human epithelial cervical cancer cells. This study was undertaken to evaluate the molecular mechanisms of fucoxanthin against human bladder cancer T24 cell line. MTT analysis results showed that 5 and 10 μM fucoxanthin inhibited the proliferation of T24 cells in a dose- and time-dependent manner accompanied by the growth arrest at G0/G1 phase of cell cycle, which is mediated by the up-regulation of p21, a cyclin-dependent kinase (CDK)-inhibitory protein and the down-regulation of CDK-2, CDK-4, cyclin D1, and cyclin E. In addition, 20 and 40 μM fucoxanthin induced apoptosis of T24 cells by the abrogation of mortalin-p53 complex and the reactivation of nuclear mutant-type p53, which also had tumor suppressor function as wild-type p53. All these results demonstrated that the anti-cancer activity of fucoxanthin on T24 cells was associated with cell cycle arrest at G0/G1 phase by up-regulation of p21 at low doses and apoptosis via decrease in the expression level of mortalin, which is a stress regulator and a member of heat shock protein 70, followed by up-regulation of cleaved caspase-3 at high doses.
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan.
authors.forename: Linbo
authors.initials: L
authors.lastname: Wang
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan.
authors.forename: Ye
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan.
authors.forename: Xuansheng
authors.initials: X
authors.lastname: Hu
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan.
authors.forename: Shuhong
authors.initials: S
authors.lastname: Li
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan Natural Product Industry of Tsukuba Co., Ltd, E-26, 1187-80 (Kenkyugakuen C43-3) East Hiratuka, Tsukuba, Ibaraki 305-0812, Japan.
authors.forename: Yuepeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan.
authors.forename: Zhongfang
authors.initials: Z
authors.lastname: Lei
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan zhang.zhenya.fu@gmail.com.
authors.forename: Zhenya
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology*; D024341:Xanthophylls / Q000494:pharmacology*
chemical_list: D018840:HSP70 Heat-Shock Proteins; D024341:Xanthophylls; C080352:mortalin; C025164:fucoxanthin; D016283:Proto-Oncogene Proteins p21(ras)
keywords: G0/G1 phase; fucoxanthin; human bladder cancer T24 cells; mortalin; p53