Synthetic retinoid CD437 induces mitochondria-mediated apoptosis in hepatocellular carcinoma cells

• Published in: Biochemical and biophysical research communications 2008-06, Vol.370 (4), p.629-633
• Main Authors: Gonda, Kazue, Tsuchiya, Hiroyuki, Sakabe, Tomohiko, Akechi, Yuji, Ikeda, Remina, Nishio, Ren, Terabayashi, Kei, Ishii, Kyoko, Matsumi, Yoshiaki, Ashla, An Afida, Okamoto, Hideharu, Takubo, Kazuko, Matsuoka, Saori, Watanabe, Yumi, Hoshikawa, Yoshiko, Kurimasa, Akihiro, Shiota, Goshi
• Format: Article
• Language: English
• Subjects: Apoptosis; bcl-2-Associated X Protein - metabolism; Carcinoma, Hepatocellular - metabolism; Caspase 3 - metabolism; Caspase 9 - metabolism; CD437; Cell Line, Tumor; Cell Proliferation - drug effects; Hepatocellular carcinoma; Humans; Liver Neoplasms - metabolism; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors; Proto-Oncogene Proteins c-bcl-2 - metabolism; Retinoids - pharmacology; Synthetic retinoid
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2008.04.008

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.