Bcl-XL protein is markedly decreased in UVB-irradiated basal cell carcinoma cell lines through proteasome-mediated degradation.

There is considerable evidence that the excessive ultraviolet radiation B (UVB) from sunlight is implicated in skin damage, ultimately inducing the death of keratinocytes. The UVB-induced apoptotic pathways are tightly regulated by the balance between pro-apoptotic and anti-apoptotic molecules. Among them, modulations of Bcl2 family proteins are important to decide the fate of UVB-irradiated cells. If the apoptotic pathway does not work properly, the damaged cells have a chance to transform into a carcinoma, such as basal cell carcinoma or squamous cell carcinoma of the skin. To develop a strategy of inducing apoptosis of skin cancer cells, the current study was performed to investigate the apoptotic pathway, especially focused on Bcl2 family proteins, in curcumin or UVB-treated basal cell carcinoma cell lines. Our data showed that the decreased proliferation rates and apoptotic DNA laddering were clearly observed in UVB irradiation, but not markedly observed in curcumin treatment. The decreased expression of Bcl-XL, which is involved in protection of apoptosis, was also clearly observed in UVB-irradiated cells without markedly changing mRNA levels. However, the expression of Bax or Bcl2 were not markedly changed by UVB-irradiation. The decreased expression of Bcl-XL protein after UVB treatment was partially restored in the presence of MG132, which is an inhibitor of proteasome, implying that the down-regulation of Bcl-XL may be regulated by the proteasome-mediated degradation. Our data demonstrated that the expression of Bcl-XL protein was decreased by proteasome-mediated degradation prior to change of mRNA level in UVB-induced apoptotic basal cell carcinoma cell lines, thereby these results will offer fundamental information to develop a strategy of inducing apoptosis of skin cancer cells.