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

Published on: January 7, 2013

Atypical protein kinase C iota expression and aurothiomalate sensitivity in human lung cancer cells

Roderick P Regala1, E Aubrey Thompson, Alan P Fields

  • 1Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, Florida 32224, USA.

Cancer Research
|July 18, 2008
PubMed

Insights

The antirheumatoid agent aurothiomalate (ATM) effectively inhibits non-small cell lung cancer (NSCLC) growth by targeting PKC iota. ATM shows promise for treating lung cancer subtypes, especially those with high PKC iota and Par6 expression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The antirheumatoid agent aurothiomalate (ATM) is identified as a potent inhibitor of oncogenic Protein Kinase C iota (PKC iota).
  • ATM's mechanism involves inhibiting the PKC iota-Par6-Rac1-Pak-Mek1,2-Erk1,2 signaling pathway, crucial for non-small cell lung cancer (NSCLC) growth.

Purpose of the Study:

  • To evaluate the growth inhibitory activity of ATM across various human lung cancer subtypes.
  • To determine the correlation between ATM sensitivity and the expression levels of PKC iota, Par6, p62, and thioredoxin reductases.
  • To assess ATM's efficacy in inhibiting tumor growth in vivo and its potential as a targeted therapy for NSCLC.

Main Methods:

  • Assessed ATM's inhibitory activity on anchorage-independent growth in a panel of human lung cancer cell lines.
  • Correlated ATM sensitivity with the expression of PKC iota, Par6, p62, and thioredoxin reductases (1 and 2).
  • Evaluated ATM's effect on tumor growth, proliferation, apoptosis, and vascularization in vivo, and compared its efficacy to standard chemotherapeutic agents.

Main Results:

  • ATM demonstrated significant growth inhibition across all tested NSCLC cell lines, with IC50 values varying widely.
  • ATM sensitivity positively correlated with PKC iota and Par6 expression, but not with p62 or thioredoxin reductase levels.
  • ATM effectively inhibited tumor growth in vivo at therapeutically relevant concentrations, reducing the proliferative index without affecting apoptosis or vascularization.

Conclusions:

  • ATM exhibits potent antitumor activity against diverse NSCLC subtypes, particularly those with high PKC iota and Par6 expression.
  • PKC iota expression levels can serve as a predictive biomarker for identifying NSCLC patients likely to respond to ATM therapy.
  • ATM represents a promising targeted therapeutic agent for NSCLC, warranting further investigation in clinical trials.

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