Role for PKC δ 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 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.
Ruvolo
Vivian R
VR
Section of Signal Transduction and Apoptosis, Hormel Institute, University of Minnesota, Austin, MN 55912, USA.
Karanjeet
Kul B
KB
Schuster
Todd F
TF
Brown
Rhoderick
R
Deng
Yibin
Y
Hinchcliffe
Edward
E
Ruvolo
Peter P
PP