Induction of endonuclease G- mediated apopotosis in human oral squamous cell carcinoma cells by protein kinase C inhibitor safingol.
PKC inhibitor safingol suppressed the growth of human oral squamous cell carcinoma ( SCC) cells significantly at concentrations that inhibit PKC isoforms. Safingol inhibited the translocation of PKC following treatment with 12-o-tetradecanoylphorbol 13-acetate (TPA) in PKC alpha-EGFP-transfected cells, but not in PKC beta-EGFP- transfected cells, indicating selective inhibition for PKC alpha in oral SCC cells. Flow cytometric analysis and DNA analysis by agarose gel electrophoresis revealed an increase in the proportion of sub-G(1) cells and DNA fragmentation in safingol-treated cells. Mitochondrial membrane potential was decreased, and cytochrome c was released from mitochondria. However, the safingol-induced cell death was not accompanied by activation of caspase 3 and cleavage of poly (ADP-ribose) polymerase (PARP). The broad-spectrum caspase inhibitor BD-fmk failed to prevent safingol-induced cell death. Another apoptogenic factor endonuclease G, but not apoptosis-inducing factor (AIF), was also released from mitochondria and translocated to the nucleus. These results suggest that PKC alpha inhibitor safingol induces an endonuclease G- mediated apoptosis in a caspase-independent manner.[1]References
- Induction of endonuclease G-mediated apopotosis in human oral squamous cell carcinoma cells by protein kinase C inhibitor safingol. Hamada, M., Sumi, T., Iwai, S., Nakazawa, M., Yura, Y. Apoptosis (2006) [Pubmed]
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