Genistein and vitamin D synergistically inhibit human prostatic epithelial cell growth

We performed studies to test synergism between the growth inhibitory effects of genistein and vitamin D compounds on prostatic epithelial cells. Isobolographic analysis demonstrated that genistein, in combination with the hormonally active form of cholecalciferol, 1alpha,25-dihydroxycholecalciferol, synergistically inhibited the growth of primary human prostatic epithelial cells (HPEC) and prostate cancer cells. Synergistic growth inhibition of HPEC was also observed between genistein and the low-calcemic vitamin D compound 25-hydroxycholecalciferol. Flow cytometry with HPEC indicated that genistein induced arrest in the G(2)M phase, whereas 1alpha,25-dihydroxycholecalciferol or 25-hydroxycholecalciferol induced arrest in the G(1/0) phase of the cell cycle. Combining genistein with either vitamin D compound resulted in both G(2)M and G(1/0) arrest in HPEC. In contrast, flow cytometry of prostate cancer cells indicated that both genistein and 1alpha,25-dihydroxycholecalciferol induced a G(1/0) arrest either alone or in combination. These are the first studies that demonstrate synergism between the prostatic cell growth inhibition elicited by genistein and that elicited by vitamin D compounds.