Skin Cancer Prevention by Carvedilol
Since approximately 90 percent of diagnosed non-melanoma skin cancers are associated with exposure to ultraviolet (UV) radiation from the sun, the primary form being UVB irradiation, we hypothesized that carvedilol will prevent UVB-induced skin carcinogenesis based on recently published results. The transformable JB6 P+ cell line, an established model for studying skin cancer promotion, was used for evaluating the impact of carvedilol on UVB-induced oxidative damage. Exposures of JB6 P+ cells to 50 - 400 mJ/cm2 UVB resulted in a dose-dependent decrease in cell viability. 25 mJ/cm2 UVB induced ~20% of cell death, and thus was chosen to study the effect of carvedilol. 0.1 to 1.0 μM carvedilol prevented UVB-induced growth inhibition and apoptosis; however, 3 to 5 μM carvedilol, although nontoxic alone, enhanced UVB-induced cell death. Contrarily, all concentrations of carvedilol tested blocked H2O2-dependent cytotoxicity of JB6 P+ cells. Thus, although both UVB and H2O2 are classic inducers of oxidative stress resulting in DNA damage and tumor promotion, carvedilol may modulate UVB and H2O2-mediated effects via different mechanisms. Cell signaling studies revealed that carvedilol inhibited EGF-inducedphosphorylation of AKT at S473 and GSK3β at S9 as well as AP-1 transactivation, which are all well-known principal mediators ofskin carcinogenesis. Since carvedilol and other β-blockers are already FDA-approved drugs, these results may be readily translated into clinical trials as a new approach for skin cancer chemoprevention.
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