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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
15:43

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

Published on: January 7, 2013

Activation of conventional PKC isoforms increases expression of the pro-apoptotic protein Bad and TRAIL receptors

Buckminster Farrow1, Robert P Thomas, Xiao-fu Wang

  • 1Department of Surgery, The University of Texas Medical Branch, Galveston, TX 77555, USA.

International Journal of Gastrointestinal Cancer
|June 10, 2003
PubMed
Abstract

Insights

Protein kinase C (PKC) stimulation in pancreatic cancer cells boosts pro-apoptotic gene Bad and TRAIL receptor expression. This suggests PKC stimulation may sensitize chemoresistant pancreatic cancers to apoptosis as an adjuvant therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Pancreatic cancer is a leading cause of cancer mortality with limited effective treatments.
  • Targeting specific signaling pathways, like protein kinase C (PKC), may enhance cancer cell sensitivity to chemotherapy.
  • Investigating PKC's role in apoptosis is crucial for developing novel pancreatic cancer therapies.

Purpose of the Study:

  • To determine the effect of protein kinase C (PKC) stimulation on apoptotic gene expression in pancreatic cancer cells.
  • To explore the potential of PKC-activating agents as an adjuvant therapy for pancreatic cancer.

Main Methods:

  • Human pancreatic cancer cells (PANC-1) were treated with PKC-stimulating agents (phorbol 12-myristate 13-acetate [PMA] or bryostatin-1).
  • Apoptosis-related gene expression was analyzed, including the pro-apoptotic gene Bad and TRAIL receptors (DR4 and DR5).
  • The role of conventional PKC isoforms and MEK pathways was investigated using specific inhibitors.

Main Results:

  • PKC stimulation with PMA or bryostatin-1 dose-dependently increased the expression of the pro-apoptotic gene Bad.
  • PKC inhibitors blocked PMA-induced Bad expression, indicating a role for conventional PKC isoforms.
  • PMA also increased TRAIL receptor (DR4 and DR5) expression, which was inhibited by PKC and MEK inhibitors.

Conclusions:

  • PKC stimulation in pancreatic cancer cells upregulates the pro-apoptotic gene Bad and TRAIL receptors (DR4 and DR5).
  • These effects are mediated through both conventional PKC- and MEK-dependent pathways.
  • PKC-stimulating agents show potential as an adjuvant therapy to sensitize chemoresistant pancreatic cancers to apoptosis.

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