Inhibition of UVB-induced nonmelanoma skin cancer: a path from tea to caffeine to exercise to decreased tissue fat.

Oral administration of green tea, black tea, or caffeine (but not the decaffeinated teas) inhibited ultraviolet B radiation (UVB)-induced skin carcinogenesis in SKH-1 mice. Studies with caffeine indicated that its inhibitory effect on the ATR/Chk1 pathway is an important mechanism for caffeine's inhibition of UVB-induced carcinogenesis. The regular teas or caffeine increased locomotor activity and decreased tissue fat. In these studies, decreased dermal fat thickness was associated with a decrease in the number of tumors per mouse. Administration of caffeine, voluntary exercise, and removal of the parametrial fat pads all stimulated UVB-induced apoptosis, inhibited UVB-induced carcinogenesis, and stimulated apoptosis in UVB-induced tumors. These results suggest that caffeine administration, voluntary exercise, and removal of the parametrial fat pads inhibit UVB-induced carcinogenesis by stimulating UVB-induced apoptosis and by enhancing apoptosis in DNA-damaged precancer cells and in cancer cells. We hypothesize that tissue fat secretes antiapoptotic adipokines that have a tumor promoting effect.