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

被引:70
作者
Gonda, Kazue [1 ]
Tsuchiya, Hiroyuki [1 ]
Sakabe, Tomohiko [1 ]
Akechi, Yuji [1 ]
Ikeda, Remina [1 ]
Nishio, Ren [1 ]
Terabayashi, Kei [1 ]
Ishii, Kyoko [1 ]
Matsumi, Yoshiaki [1 ]
Ashla, An Afida [1 ]
Okamoto, Hideharu [2 ]
Takubo, Kazuko [2 ]
Matsuoka, Saori [1 ,3 ]
Watanabe, Yumi [1 ,4 ]
Hoshikawa, Yoshiko [1 ]
Kurimasa, Akihiro [1 ]
Shiota, Goshi [1 ]
机构
[1] Tottori Univ, Grad Sch Med, Dept Genet Med & Regenerat Therapeut, Div Mol & Genet Med, Yonago, Tottori 6838504, Japan
[2] Tottori Univ, Dept Med Sensory & Motor Organs, Div Oral & Maxillofacial Biopathol Surg, Yonago, Tottori 6838504, Japan
[3] Shimane Prefectural Ctr Hosp, Izumo, Shimane, Japan
[4] Watanabe Children & Ladies Clin, Izumo, Shimane, Japan
关键词
synthetic retinoid; CD437; apoptosis; hepatocellular carcinoma; mitochondria;
D O I
10.1016/j.bbrc.2008.04.008
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
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 apoplosis 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 BcI-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. (c) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:629 / 633
页数:5
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