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

The synthetic Vitamin A analog fenretinide is a promising chemotherapeutic agent. In the current paper, the role of PKC was examined in fenretinide-induced apoptosis in lymphoid leukemia cells. Levels of proapoptotic cleaved PKC positively correlated with drug sensitivity. Fenretinide promoted react...

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Veröffentlicht in:Journal of signal transduction 2010-06, Vol.2010, p.1-15
Hauptverfasser: Ruvolo, Vivian R., Karanjeet, Kul B., Schuster, Todd F., Brown, Rhoderick, Deng, Yibin, Hinchcliffe, Edward, Ruvolo, Peter P.
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container_issue
container_start_page 1
container_title Journal of signal transduction
container_volume 2010
creator Ruvolo, Vivian R.
Karanjeet, Kul B.
Schuster, Todd F.
Brown, Rhoderick
Deng, Yibin
Hinchcliffe, Edward
Ruvolo, Peter P.
description The synthetic Vitamin A analog fenretinide is a promising chemotherapeutic agent. In the current paper, the role of PKC was examined in fenretinide-induced apoptosis in lymphoid leukemia cells. Levels of proapoptotic cleaved PKC positively correlated with drug sensitivity. Fenretinide promoted reactive oxygen species (ROS) generation. The antioxidant Vitamin C prevented fenretinide-induced PKC cleavage and protected cells from fenretinide. Suppression of PKC 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 as cleavage of the kinase correlated with loss of MCL-1 even in cells when JNK was not activated. These results suggest that PKC may play a complex role in fenretinide-induced apoptosis and may be targeted in antileukemia strategies that utilize fenretinide.
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subjects Apoptosis
Cancer
Kinases
Proteins
title Role for PKC in Fenretinide-Mediated Apoptosis in Lymphoid Leukemia Cells
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