The objective of the present study was to test the hypothesis that
Calcidiol derivative B3CD qualifies as a potential anti-
cancer drug in vivo employing an
ovarian cancer xenograft model in mice. In addition, the selectivity of B3CD on viability and proliferation of
platinum-resistant human
ovarian cancer cell lines in comparison to control cell lines was analyzed in vitro. B3CD displayed cell line-specific cytotoxicity screened against a panel of ovarian and other
carcinoma cell lines, endothelial and control cells. B3CD, at sub-cytotoxic concentrations, revealed stronger effects on the proliferation of SKOV-3
ovarian cancer cells vs. primary fibroblasts as determined by
BrdU incorporation analysis. Treatment with B3CD at 0.5 microM resulted in highly condensed
chromatin and fragmented nuclei in SKOV-3 cells but not in primary fibroblasts. B3CD induced cell death at low drug concentrations (< or = 0.5 microM) in SKOV-3
ovarian cancer cells is mediated by the
p38 MAPK signaling pathway: B3CD induced
p38 MAPK expression and activation in SKOV-3 cells and inhibition of p38 signaling counteracted B3CD induced cell death in vitro. An
ovarian cancer cell animal model (human SKOV-3 cell derived xenografts in nude mice) revealed that
tumor growth in few B3CD treated mice accelerated while the majority of B3CD treated mice displayed delayed
tumor growth or full
tumor regression. B3CD possesses anti-
ovarian cancer properties in vitro and in vivo. We propose the further development of non-calcemic bromoacetoxy derivatives of
vitamin D(3) as potential anti-
cancer therapeutics.