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

Abstract EN

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.