Abstract
1,25-Dihydroxyvitamin D 3 (1,25(OH) 2D 3), the biologically active form of vitamin D has strong antiproliferative effects in cancer cells. But it is highly toxic at therapeutic doses. We have observed that 25-hydroxyvitamin D 3-3-bromoacetate (25-OH-D 3-3-BE), a derivative of 25-hydroxyvitamin D 3, the pro-hormonal form of 1,25(OH) 2D 3 has strong growth-inhibitory and proapoptotic properties in hormone-sensitive and hormone-refractory prostate cancer cells. In the present investigation we demonstrate that the antiproliferative effect of 25-OH-D 3-3-BE is predominantly mediated by VDR in ALVA-31 prostate cancer cells. In other mechanistic studies we show that the proapoptotic property of 25-OH-D 3-3-BE is related to the inhibition of phosphorylation of Akt, a pro-survival protein. Furthermore, we carried out cellular uptake and serum stability studies of 25-OH-D 3-3-BE to demonstrate potential therapeutic applicability of 25-OH-D 3-3-BE in hormone-sensitive and hormone-insensitive prostate cancer.
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