Role of testosterone, estradiol, and insulin in diet- and exercise-induced reductions in serum-stimulated prostate cancer cell growth in vitro

Prostate cancer risk is associated with a high fat diet and a sedentary lifestyle. Placing men on a low fat diet-and-exercise intervention reduces serum hormones, including estradiol, insulin, and free testosterone, that may play a role in prostate cancer growth. Eight men participated in a low fat diet-and-exercise program for a mean of 14.2 yr, and LNCaP cell growth in culture was measured in medium supplemented with 10% of each subject's serum as well as with testosterone, estradiol, and insulin added singly or in combination. These results were compared in the fetal bovine serum (FBS)-stimulated growth and cell growth in serum obtained from a control group of 14 overweight men. In separate tissue culture experiments, LNCaP and PC-3 cell growth was also measured in response to the addition of testosterone, estradiol, or insulin to steroid-stripped FBS. LNCaP cell growth in medium with subject serum was 40% less than in FBS-stimulated medium and 49% less than in medium with serum from control, overweight men. Addition of testosterone, estradiol, and insulin to serum from diet-and-exercise subjects significantly stimulated LNCaP cell growth in vitro but accounted for only about half of the difference between the control and diet-and-exercise subjects. Thus other serum changes must also account for the significant reduction in LNCaP cell growth observed using medium with serum from the diet-and-exercise subjects in the cell culture assay.