title: Synthetic retinoid CD437 induces mitochondria-mediated apoptosis in hepatocellular carcinoma cells.
abstract: Retinoids play an important role in the regulation of cell growth and death. Synthetic retinoid CD437 reportedly induces apoptosis in various cancer cell lines. However, the mechanism of inducing apoptosis in hepatocellular carcinoma (HCC) cells by this agent remains to be clarified. In this study, we investigated the signaling pathway by which CD437 induces apoptosis in HCC cell lines. Apoptosis of six human HCC cell lines was induced by treatment with CD437. Caspase-3 and -9 were activated by CD437, suggesting that the apoptosis is mediated by mitochondrial pathways. Consistent with these findings, the treatment with CD437 upregulated Bax protein, downregulated Bcl-2 protein and released cytochrome c into the cytoplasm. Moreover, rhodamine123 staining revealed mitochondrial depolarization in the cells treated with CD437. These data of the present study suggest that CD437 induces apoptosis in HCC cells via mitochondrial pathways.
authors.affiliation: Division of Molecular and Genetic Medicine, Department of Genetic Medicine and regenerative Therapeutics, Graduate School of Medicine, Tottori University, Nishi-cho 86, Yonago 683-8504, Japan.
authors.forename: Kazue
authors.initials: K
authors.lastname: Gonda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsuchiya
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Sakabe
authors.forename: Yuji
authors.initials: Y
authors.lastname: Akechi
authors.forename: Remina
authors.initials: R
authors.lastname: Ikeda
authors.forename: Ren
authors.initials: R
authors.lastname: Nishio
authors.forename: Kei
authors.initials: K
authors.lastname: Terabayashi
authors.forename: Kyoko
authors.initials: K
authors.lastname: Ishii
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Matsumi
authors.forename: An Afida
authors.initials: AA
authors.lastname: Ashla
authors.forename: Hideharu
authors.initials: H
authors.lastname: Okamoto
authors.forename: Kazuko
authors.initials: K
authors.lastname: Takubo
authors.forename: Saori
authors.initials: S
authors.lastname: Matsuoka
authors.forename: Yumi
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Hoshikawa
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kurimasa
authors.forename: Goshi
authors.initials: G
authors.lastname: Shiota
mesh_terms: D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D012176:Retinoids / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C099555:CD 437; D019253:Proto-Oncogene Proteins c-bcl-2; D012176:Retinoids; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D053453:Caspase 9