Role for PKC δ in Fenretinide-Mediated Apoptosis in Lymphoid Leukemia Cells

• Published in: Journal of signal transduction 2010, Vol.2010 (2010), p.1-15
• Main Authors: Ruvolo, Vivian R., Karanjeet, Kul B., Schuster, Todd F., Brown, Rhoderick E., Deng, Yibin, Hinchcliffe, Edward, Ruvolo, Peter P.
• Format: Article
• Language: English
• ISSN: 2090-1739; 2090-1747

The synthetic Vitamin A analog fenretinide is a promising chemotherapeutic agent. In the current paper, the role of PKC δ was examined in fenretinide-induced apoptosis in lymphoid leukemia cells. Levels of proapoptotic cleaved PKC δ positively correlated with drug sensitivity. Fenretinide promoted reactive oxygen species (ROS) generation. The antioxidant Vitamin C prevented fenretinide-induced PKC δ cleavage and protected cells from fenretinide. Suppression of PKC δ expression by shRNA sensitized cells to fenretinide-induced apoptosis possibly by a mechanism involving ROS production. A previous study demonstrated that fenretinide promotes degradation of antiapoptotic MCL-1 in ALL cells via JNK. Now we have found that fenretinide-induced MCL-1 degradation may involve PKC δ as cleavage of the kinase correlated with loss of MCL-1 even in cells when JNK was not activated. These results suggest that PKC δ may play a complex role in fenretinide-induced apoptosis and may be targeted in antileukemia strategies that utilize fenretinide.