4-OH tamoxifen does not interfere with bicalutamide inhibitory effects on human prostatic cancer cells in vitro.

BACKGROUND: The present study was aimed at investigating the effects of the co-administration of 4-OH Tamoxifen (4HT) and bicalutamide (BIC) on the human prostate cancer cell line LNCaP in vitro. MATERIALS AND METHODS: The LNCaP FGC prostate cancer cell line was grown in vitro within a three-dimensional matrix formed by collagen gel under dihydrotestosterone (DHT) (0.1 nM) stimulation. Cells were incubated in the presence either of BIC at escalating concentrations (1 nM; 100 nM; 10 microM) or 4HT Tamoxifen (10 nM; 100 nM) or both compounds at the different concentrations studied. The cells were incubated for 144 hours, and growth was evaluated in non trypsinised cells by crystal violet vital dye staining assay. RESULTS: BIC appeared to exert a dose-dependent inhibitory action, with the maximum inhibitory effect achieved by the 10 microM concentration. A comparable inhibitory effect was also observed after exposure to 4HT at both doses tested. No statistically significant interference was observed when BIC was combined with 4HT. CONCLUSION: 4HT, even at the higher concentration employed here, showed no major interference with the inhibitory effects of BIC.

FMS*Calciumfluor specifically increases mRNA levels and induces signaling via MAPK 42,44 and not FAK in differentiating rat osteoblasts.

The homeopathic compound of resonance FMS*Calciumfluor (FMS*) reportedly promotes osteogenic differentiation of rat pre-osteoblasts in vitro. Here, we show that the continuous exposure of differentiating rat osteogenic cells (ROB) to FMS* modulates the level of expression of mRNAs for 7 of the 8 osteogenic markers tested. Alkaline phosphatase (AP), osteocalcin (OC), metalloproteinases (MMP-2 and -14), procollagenase C (BMP-1), biglycan (BG) and integrin 1 are expressed at higher levels in FMS*-treated osteoblasts than in control cultures. MMP-2 and -14 mRNA are not down-modulated at mineralization. Also, the pattern of expression induced by FMS* for some of these genes (BMP-1, BG and integrin 1) is changed, but collagen type I (Coll I) mRNA levels are not affected by treatment with FMS*. This suggests that FMS* modulates mRNA levels and that this is not generalized, but gene(s) specific. We also report that exposure to FMS* rapidly and transiently induces activation of mitogen-activated protein kinases (MAPKs) 42,44 in populations of early osteoblasts, but not in pre-osteoblasts, with a cell differentiation stage-dependent and pertussis toxin (PTX)-sensitive response. Subsequent to FMS* MAPK signaling activation, an increase in AP and MMP-14 mRNA is detected, which is also inhibited by PTX, suggesting that FMS* activation of MAPK signaling could be an early event required for the induction of these genes. Exposure to FMS* does not cause changes in the activity of p125 (FAK)-mediated signaling.