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CD437 induces apoptosis in ovarian adenocarcinoma cells via ER stress signaling.

Watanabe Y, Tsuchiya H, Sakabe T, Matsuoka S, Akechi Y, Fujimoto Y, Yamane K, Ikeda R, Nishio R, Terabayashi K, Ishii K, Gonda K, Matsumi Y, Ashla AA, Okamoto H, Takubo K, Tomita A, Hoshikawa Y, Kurimasa A, Itamochi H, Harada T, Terakawa N, Shiota G

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.

A synthetic retinoid, CD437, has been shown to exert potent anti-tumor activity against various types of cancer cell lines, regardless of their sensitivities to natural retinoids. We herein demonstrate that CD437 induces endoplasmic reticulum (ER) stress, including the up-regulation of CHOP, BIP and GADD34 mRNA through ER stress transducer (PERK and IRE1alpha) activation in an ovarian adenocarcinoma cell line, SKOV3. It was also shown that CD437 induced the CHOP and GADD34 expressions in another four ovarian adenocarcinoma cell lines, indicating that CD437 functions as an ER stress inducer in these cell lines. Moreover, the siRNA-mediated knockdown of inducible CHOP expression prevented the cytotoxic effect of CD437. These results suggest that ER stress plays an important role in the mechanism by which CD437 induces apoptosis in ovarian adenocarcinoma cells.

Published 8 January 2008 in Biochem Biophys Res Commun, 366(3): 840-7.
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