The effect of oral
caffeine or voluntary running wheel exercise (RW) alone or in combination on the progression of human
androgen-dependent LNCaP prostate
tumors to
androgen independence in male
severe combined immunodeficiency mice was determined. The mice were injected subcutaneously with LNCaP cells, and when the
tumors reached a moderate size, the mice were surgically castrated and treated with
caffeine (0.40 mg/ml
drinking water) or RW alone or in combination for 42 days. We found that
caffeine administration or RW inhibited the progression and growth of
androgen-dependent LNCaP
tumors to
androgen independence, and a combination of the 2 regimens was more effective than the individual regimens alone. The ratios of the percent mitotic cells/
caspase-3 positive cells in
tumors from the
caffeine-treated, RW-treated, or combination-treated mice were decreased by 34%, 38%, and 52%, respectively.
Caffeine treatment increased the percentage of mitotic
tumor cells undergoing apoptosis (lethal mitosis) whereas RW inhibited the increase in
interleukin-6 that occurred during the progression of LNCaP
tumors from
androgen dependence to
androgen independence. Our results indicate that
oral administration of
caffeine in combination with voluntary exercise may be an effective strategy for the prevention of
prostate cancer progression from
androgen dependence to
androgen independence.