Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2052870 | FEBS Letters | 2006 | 6 Pages |
Doxorubicin, cis-diamminedichloroplatinum (II) and 5-fluorouracil used in chemotherapy induce apoptosis in Hep3B cells in the absence of p53, p73, and functional Fas. Since mediators remain unknown, the requirement of PKC delta (PKCδ) and c-Abl was investigated. Suppression of c-Abl or PKCδ expression using SiRNAs impaired PARP cleavage, Gleevec® and/or rottlerin inhibited the induction of the subG1 phase and the increase of reactive oxygen species level. Co-precipitations and phosphorylations to mitochondria of c-Abl, PKCδ and Bcl-XL/s were induced. A depolarization of the mitochondrial membrane and activations of caspase-2 and -9 were observed. We propose that, in the absence of p53, p73 and Fas, genotoxic drugs could require both PKCδ and c-Abl to induce apoptosis through the mitochondrial pathway.