Table of Contents
Journal of Signal Transduction
Volume 2010, Article ID 584657, 15 pages
http://dx.doi.org/10.1155/2010/584657
Research Article

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

1Section of Signal Transduction and Apoptosis, Hormel Institute, University of Minnesota, Austin, MN 55912, USA
2Section of Cellular Dynamics, Hormel Institute, University of Minnesota, Austin, MN 55912, USA
3Section of Membrane Biochemistry, Hormel Institute, University of Minnesota, Austin, MN 55912, USA
4Section of Cell Death and Cancer Genetics, Hormel Institute, University of Minnesota, Austin, MN 55912, USA
5Department of Stem Cell Transplantation, MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, Tex 77030, USA

Received 10 November 2009; Accepted 17 March 2010

Academic Editor: Alakananda Basu

Copyright © 2010 Vivian R. Ruvolo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.