Resveratrol pretreatment desensitizes AHTO-7 human osteoblasts to growth stimulation in response to carcinoma cell supernatants

Resveratrol, a natural phytoestrogen, has been reported to promote differen tiation of murine MC3T3-E1 osteoblasts and to inhibit proliferation of pros tate cancer cell lines. In the present study we tested the effects of resve ratrol on the increased proliferation of human AHTO-7 osteoblastic cell lin e induced by conditioned media (CM) from a panel of carcinoma cell lines. T his compound was found to modulate AHTO-7 proliferation in a tamoxifen-sens itive mechanism at lower concentrations, but failed to induce the osteoblas t differentiation marker alkaline phosphatase (ALP) in contrast to vitamin D3. The proliferative response of AHTO-7 cells to conditioned media from ca rcinoma cell lines was diminished (30-71.4% inhibition) upon pretreatment w ith 0.5 CIM resveratrol. Highest inhibition was demonstrated for pancreas ( BxPC3, Panc-1), breast (ZR75-1) and renal (ACHN) carcinoma cell line supern atants whereas the effect on colon carcinoma (SW620, Colo320DM) cell CM and prostate cancer (PC3, DU145 and LNCaP) CM was less pronounced. Direct addi tion of resveratrol affected only supernatants of cell lines (<25% inhibiti on) exhibiting growth stimulatory activity for normal WI-38 lung fibroblast s. Resveratrol inhibited proliferation of DU145 and LNCaP cells in concentr ations exceeding 5 mu M, altered cell cycle distribution of all prostate ca ncer cell lines in concentrations as low as 0.5 mu M, but did not inhibit t he production of osteoblastic factors by these lines. In conclusion, resver atrol failed to induce ALP activity as marker of osteoblast differentiation in human osteoblastic AHTO-7 cells, however, inhibited their response to o steoblastic carcinoma-derived growth factors in concentrations significantl y lower than those to reduce growth of cancer cells, thus effectively modul ating tumor - osteoblast interaction.