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The effect of the hydroxymethylglutaryl-CoA (HMG-CoA) inhibitor lovastatin on the UVA-induced photocytotoxicity has been investigated in cultured human N.C.T.C. 2544 keratinocytes. In the absence of irradiation, 5 x 10(-7) M lovastatin did not exhibit any significant cytotoxic effect towards this cell line. Although the drug cannot act as a photosensitizer, because it does not absorb in the UVA range, it markedly increased the UVA-induced cellular damage (about 70% reduction in cell viability at 5 x 10(-7) M). This effect was not accompanied by an increase in the lipid peroxidation product content of cells as compared with treatment with UVA alone. Medium supplementation with 0.01 mg/ml free cholesterol totally prevented the enhancement of UVA photocytotoxicity induced by lovastatin. A protective effect was also observed when cells were supplemented with an amount of low-density lipoprotein giving the same cholesterol concentration in the culture medium. Finally, E64 [L-trans-epoxysuccinyl-leucylamido-(4-guanidino)-butane], a lysosomal cathepsin inhibitor, also prevents the cell death induced by UVA in cells treated with lovastatin. These results suggest that HMG-CoA reductase inhibitors could increase the sensitivity of skin cells to UVA radiation, and that this phenomenon is related to lysosomal enzyme release.

biochemical journal

Lovastatin enhances the photocytotoxicity of UVA radiation towards cultured N.C.T.C. 2544 human keratinocytes: prevention by cholesterol supplementation and by a cathepsin inhibitor