Article

Apoptosis

, Volume 11, Issue 1, pp 47-56

First online:

Induction of endonuclease G-mediated apopotosis in human oral squamous cell carcinoma cells by protein kinase C inhibitor safingol

  • M. HamadaAffiliated withDepartment of Oral and Maxillofacial Surgery II, Osaka University Graduate School of Dentistry
  • , T. SumiAffiliated withDepartment of Oral and Maxillofacial Surgery II, Osaka University Graduate School of Dentistry
  • , S. IwaiAffiliated withDepartment of Oral and Maxillofacial Surgery II, Osaka University Graduate School of Dentistry
  • , M. NakazawaAffiliated withDepartment of Oral and Maxillofacial Surgery II, Osaka University Graduate School of Dentistry
  • , Y. YuraAffiliated withDepartment of Oral and Maxillofacial Surgery II, Osaka University Graduate School of DentistryDepartment of Oral and Maxillofacial Surgery II, Osaka University Graduate School of Dentistry Email author 

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Abstract

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.

Keywords

apoptosis endonuclease G mitochondria oral cancer PKC inhibitor safingol