Synthetic retinoid CD437 induces mitochondria-mediated apoptosis in hepatocellular carcinoma cells.
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.
Gonda
Kazue
K
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.
Tsuchiya
Hiroyuki
H
Sakabe
Tomohiko
T
Akechi
Yuji
Y
Ikeda
Remina
R
Nishio
Ren
R
Terabayashi
Kei
K
Ishii
Kyoko
K
Matsumi
Yoshiaki
Y
Ashla
An Afida
AA
Okamoto
Hideharu
H
Takubo
Kazuko
K
Matsuoka
Saori
S
Watanabe
Yumi
Y
Hoshikawa
Yoshiko
Y
Kurimasa
Akihiro
A
Shiota
Goshi
G
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
C099555:CD 437; D019253:Proto-Oncogene Proteins c-bcl-2; D012176:Retinoids; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D053453:Caspase 9