['To investigate the effect and molecular mechanisms of action of Vitamin D(3) (VD(3) ) as a neo-adjunctive agent before cryosurgery in an effort to increase treatment efficacy for prostate cancer (CaP). To eliminate the potential for disease recurrence that exists at the periphery of the freeze lesion, where temperatures may be insufficient to destroy both androgen-sensitive (AS) and androgen-insensitive (AI) CaP.', 'Human CaP cells, LNCaP, were each genetically altered to express the AS and AI phenotypes and subjected to VD(3) treatment and freezing in an in vitro and tissue-engineered model. Cell viability, caspase inhibitor and western blot studies were used to determine the basis of the different responses of AI and AS cells to VD(3) cryosensitization.', 'VD(3) was found to be a highly effective cryosensitizer, resulting in a >50% overall increase in cell death after -15 °C freezing. Fluorescence microscopy, western blot analysis and caspase protease assays confirmed that the increased activation of apoptosis was modulated through a mitochondrial-mediated pathway. Caspase inhibition studies showed that apoptosis played an integral role in cell death, with VD(3) cryosensitivation-induced apoptotic events responsible for >30% of the overall cell death after -15 °C freezing.'] Does vitamin D ( 3 ) cryosensitization increase prostate cancer susceptibility to cryoablation via mitochondrial-mediated apoptosis and necrosis?