Anticancer research

Protein kinase C delta-mediated cytoskeleton remodeling is involved in aloe-emodin-induced photokilling of human lung cancer cells.

PMID 22993309


Photodynamic therapy is becoming a widely accepted form of cancer treatment using a photosensitizing agent and light. Our previous study has demonstrated that photoactivated aloe-emodin induced anoikis and changes in cell morphology, which were in part mediated through its effect on cytoskeleton in lung carcinoma H460 cells. However, the molecular mechanisms of these photoactivated aloe-emodin-induced changes remain unknown. The present study demonstrated that the expression of protein kinase Cδ (PKCδ) was triggered by aloe-emodin and irradiation in H460 cells. Furthermore, the photoactivated aloe-emodin-induced cell death and translocation of PKCδ from the cytosol to the nucleus was found to be significantly inhibited by rottlerin, a PKCδ-selective inhibitor. Western blot analysis demonstrated that rottlerin also reversed the decrease in protein expression of cytoskeleton-related proteins, such as rat sarcoma (RAS), ras homolog gene family member A (RHO), p38, heat shock protein 27 (HSP27), focal adhesion kinase (FAK), α-actinin and tubulin, induced by photoactivated aloe-emodin. Our findings suggest that the regulation of cytoskeleton-related proteins mediated by PKCδ may be the mechanisms for the protective effects of rottlerin against the photoactivated aloe-emodin induced H460 cell death.