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Ectopic expression of protein kinase C-β sensitizes head and neck squamous cell carcinoma to diterpene esters

Ryan A Adams1, Marjorie M A D'Souza2, Carly J Pierce2

  • 1Department of Otolaryngology, Head and Neck Surgery, Princess Alexandra Hospital, Woolloongabba, Brisbane, Queensland, Australia School of Medicine, University of Queensland, Brisbane, Queensland, Australia Drug Discovery Group, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.

Anticancer Research
|March 10, 2015
PubMed
Abstract

Insights

Re-expressing Protein kinase C beta (PKCβ) in head and neck squamous cell carcinoma (SCC) cells significantly increases their sensitivity to cytotoxic compounds like TPA and PEP005. This finding suggests potential therapeutic benefits for malignancies expressing PKCβ.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Solid malignancies, including head and neck squamous cell carcinoma (SCC), present complex therapeutic challenges.
  • Protein kinase C (PKC) isoforms play a role in cellular signaling pathways relevant to cancer progression.
  • Understanding the impact of specific PKC isoform expression on treatment response is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the effect of re-expressing specific Protein kinase C (PKC) isoforms in head and neck SCC cell lines.
  • To determine how PKC isoform re-expression influences sensitivity to known PKC activators, such as 12-O-tetradecanoylphorbol-13-acetate (TPA) and PEP005.
  • To explore the potential therapeutic implications of targeting PKC pathways in solid tumors.

Main Methods:

  • Constitutive expression of PKC isoforms was analyzed in six head and neck SCC cell lines.
  • Cytotoxicity assays were performed using the phorbol ester TPA and the diterpene ester PEP005.
  • Viral transduction was employed to re-express PKCβ isoforms in selected cell lines, followed by sensitivity quantification.

Main Results:

  • Head and neck SCC cell lines exhibited resistance to TPA and PEP005, with high IC50 values (>1,000 ng/ml).
  • Cell lines (CAL-27 and FaDu) engineered to re-express PKCβI and -βII isoforms showed significantly increased sensitivity.
  • Re-expressing PKCβ isoforms resulted in low IC50 values (1-5 ng/ml) for both TPA and PEP005.

Conclusions:

  • Re-expression of PKCβ isoforms renders head and neck SCC cells over a thousand times more sensitive to cytotoxic PKC activators.
  • The PKCβ isoform is critical in tumor progression and influences cellular response to specific therapeutic agents.
  • These findings support the potential utility of TPA and PEP005, particularly in combination therapy, for malignancies expressing PKCβ.
Keywords:
HNSCCPEP005Protein kinase CTPAditerpene

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