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Vitamin D 3  (VD 3 ) is an effective adjunctive agent, enhancing the destructive effects of freezing in prostate cancer cryoablation studies. We investigated whether dose escalation of VD 3  over several weeks, to model the increase in physiological VD 3  levels if an oral supplement were prescribed, would be as or more effective than a single treatment 1 to 2 days prior to freezing. PC-3 cells in log phase growth to model aggressive, highly metabolically active prostate cancer were exposed to a gradually increasing dose of VD 3  to a final dose of 80 nM over a 4-week period, maintained for 2 weeks at 80 nM, and then exposed to mild sublethal freezing temperatures. Results demonstrate that both acute 24-hour exposure to 80 nM VD 3  and dose escalation resulted in enhanced cell death following freezing at −15°C or colder, with no significant differences between the 2 exposure regimes. Apoptotic analysis within the initial 24-hour period postfreeze revealed that VD 3  treatment induced both caspase 8- and 9-mediated cell death, most notably in caspase 8 at 8-hour postfreeze. These results indicate that both the intrinsic and extrinsic apoptotic pathways are involved in VD 3  sensitization prior to freezing. Additionally, both acute and gradual dose escalation regimes of VD 3  exposure increase prostate cancer cell sensitivity to mild freezing. Importantly, this study expands upon previous reports and suggests that the combination of VD 3  and freezing may offer an effective treatment for both slow growth and highly aggressive prostate cancers.

Dose Escalation of Vitamin D3 Yields Similar Cryosurgical Outcome to Single Dose Exposure in a Prostate Cancer Model

Dose Escalation of Vitamin D₃ Yields Similar Cryosurgical Outcome to Single Dose Exposure in a Prostate Cancer Model