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Use of 1,25α dihydroxyvitamin D3 as a cryosensitizing agent in a murine prostate cancer model.

Publication ,  Journal Article
Santucci, KL; Snyder, KK; Baust, JM; Van Buskirk, RG; Mouraviev, V; Polascik, TJ; Gage, AA; Baust, JG
Published in: Prostate Cancer Prostatic Dis
June 2011

Cryotherapy has emerged as a primary treatment option for prostate cancer (CaP); however, incomplete ablation in the periphery of the cryogenic lesion can lead to recurrence. Accordingly, we investigated the use of a non-toxic adjunctive agent, vitamin D3 (VD3), with cryotherapy to sensitize CaP to low temperature-induced, non-ice rupture-related cell death. VD3 (calcitriol) has been identified as a possible adjunct in the treatment of cancer because of its antiproliferative and antitumorigenic properties. This study aimed to identify the cellular responses and molecular pathways activated when VD3 (calcitriol) is combined with cryotherapy in a murine CaP model. Single freeze-thaw events above -15 °C had little effect on cancer cell viability; however, pretreatment with calcitriol in conjunction with cryo significantly increased cell death. The -15 °C calcitriol combination increased cell death to 55% following a single freeze compared with negligible cell loss by freezing or calcitriol alone. Repeated cryo combination yielded 90% cell death compared with 65% in dual freeze-only cycles. Western blot analysis following calcitriol cryosensitization regimes confirmed the activation of apoptosis. Specifically, proapoptotic Bid and procaspase-3 were found to decrease at 1 h following combination treatment, indicating cleavage to the active forms. A parallel in vivo study confirmed the increased cell death when combining cryotherapy with calcitriol pretreatment. The development of an adjunctive therapy combining calcitriol and cryotherapy represents a potentially highly effective, less toxic, minimally invasive treatment option. These results suggest a role for calcitriol and cryo as a combinatorial treatment for CaP, with the potential for clinical translation.

Duke Scholars

Published In

Prostate Cancer Prostatic Dis

DOI

EISSN

1476-5608

Publication Date

June 2011

Volume

14

Issue

2

Start / End Page

97 / 104

Location

England

Related Subject Headings

  • Urology & Nephrology
  • Tumor Cells, Cultured
  • Prostatic Neoplasms
  • Mice
  • Male
  • Humans
  • Disease Models, Animal
  • Cryotherapy
  • Combined Modality Therapy
  • Chemotherapy, Adjuvant
 

Citation

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Santucci, K. L., Snyder, K. K., Baust, J. M., Van Buskirk, R. G., Mouraviev, V., Polascik, T. J., … Baust, J. G. (2011). Use of 1,25α dihydroxyvitamin D3 as a cryosensitizing agent in a murine prostate cancer model. Prostate Cancer Prostatic Dis, 14(2), 97–104. https://doi.org/10.1038/pcan.2010.52
Santucci, K. L., K. K. Snyder, J. M. Baust, R. G. Van Buskirk, V. Mouraviev, T. J. Polascik, A. A. Gage, and J. G. Baust. “Use of 1,25α dihydroxyvitamin D3 as a cryosensitizing agent in a murine prostate cancer model.Prostate Cancer Prostatic Dis 14, no. 2 (June 2011): 97–104. https://doi.org/10.1038/pcan.2010.52.
Santucci KL, Snyder KK, Baust JM, Van Buskirk RG, Mouraviev V, Polascik TJ, et al. Use of 1,25α dihydroxyvitamin D3 as a cryosensitizing agent in a murine prostate cancer model. Prostate Cancer Prostatic Dis. 2011 Jun;14(2):97–104.
Santucci, K. L., et al. “Use of 1,25α dihydroxyvitamin D3 as a cryosensitizing agent in a murine prostate cancer model.Prostate Cancer Prostatic Dis, vol. 14, no. 2, June 2011, pp. 97–104. Pubmed, doi:10.1038/pcan.2010.52.
Santucci KL, Snyder KK, Baust JM, Van Buskirk RG, Mouraviev V, Polascik TJ, Gage AA, Baust JG. Use of 1,25α dihydroxyvitamin D3 as a cryosensitizing agent in a murine prostate cancer model. Prostate Cancer Prostatic Dis. 2011 Jun;14(2):97–104.

Published In

Prostate Cancer Prostatic Dis

DOI

EISSN

1476-5608

Publication Date

June 2011

Volume

14

Issue

2

Start / End Page

97 / 104

Location

England

Related Subject Headings

  • Urology & Nephrology
  • Tumor Cells, Cultured
  • Prostatic Neoplasms
  • Mice
  • Male
  • Humans
  • Disease Models, Animal
  • Cryotherapy
  • Combined Modality Therapy
  • Chemotherapy, Adjuvant