, Volume 11, Issue 1, pp 47–56

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 α-EGFP-transfected cells, but not in PKC β-EGFP- transfected cells, indicating selective inhibition for PKC α in oral SCC cells. Flow cytometric analysis and DNA analysis by agarose gel electrophoresis revealed an increase in the proportion of sub-G1 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 α inhibitor safingol induces an endonuclease G- mediated apoptosis in a caspase-independent manner.


apoptosis endonuclease G mitochondria oral cancer PKC inhibitor safingol 



apoptosis-inducing factor


poly (ADP-ribose) polymerase


protein kinase C α


squamous cell carcinoma


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Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • M. Hamada
    • 1
  • T. Sumi
    • 1
  • S. Iwai
    • 1
  • M. Nakazawa
    • 1
  • Y. Yura
    • 1
    • 2
  1. 1.Department of Oral and Maxillofacial Surgery IIOsaka University Graduate School of DentistryOsakaJapan
  2. 2.Department of Oral and Maxillofacial Surgery IIOsaka University Graduate School of DentistryOsakaJapan

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