Involvement of proteolytic activation of PKCδ in cisplatin-induced apoptosis in human small cell lung cancer H69 cells

Shalini D. Persaud, Van Hoang, Jie Huang, Alakananda Basu

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Proteolytic activation of protein kinase C δ (PKCδ) has been associated with apoptosis induced by the DNA damaging agent cisplatin. In cells undergoing apoptosis, caspase-3 cleaves PKCδ at the site DMQD4-N to generate a 40-kDa catalytic fragment. We have previously shown that the PKC signal transduction pathway regulates sensitivity of human small cell lung cancer H69 cells to cisplatin. In the present study, we have investigated if proteolytic activation of PKCδ is essential for cisplatin-induced apoptosis in H69 cells. The caspase cleavage-resistant mutant PKCδ (DMQA) was generated by mutating the aspartate residue at the site of proteolysis DMQD1N to alanine (D330A), and the wild-type and mutant PKCδ were introduced into H69 cells. Cisplatin induced a substantial increase in PKCδ catalytic fragment in H69 cells overexpressing PKCδ (H69/δ, and the level of PKCδ catalytic fragment in H69 cells expressing DMQA mutant (H69/DMQA) was equivalent to that in H69 cells. However, the cleavage of poly(ADP-ribose) polymerase (PARP), another substrate for caspase-3, was similar in cells overexpressing wild-type PKCδ and DMQA mutant PKCδ. The ability of cisplatin to induce mitochondrial depolarization and cell death was also equivalent among the cell lines tested. These results suggest that the proteolytic fragment of PKCδ does not play a critical role in the induction of apoptosis in H69 cells.

Original languageEnglish
Pages (from-to)149-154
Number of pages6
JournalInternational journal of oncology
Volume27
Issue number1
DOIs
StatePublished - Jul 2005

Keywords

  • Apoptosis
  • Cisplatin
  • DNA damage
  • PKCδ
  • Small cell lung cancer

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