Cancer Chemotherapy and Pharmacology

, Volume 62, Issue 5, pp 787–797

Toxicity and antitumor activity of the vitamin D analogs PRI-1906 and PRI-1907 in combined treatment with cyclophosphamide in a mouse mammary cancer model

  • Joanna Wietrzyk
  • Dmitry Nevozhay
  • Magdalena Milczarek
  • Beata Filip
  • Andrzej Kutner
Original Article

DOI: 10.1007/s00280-007-0666-6

Cite this article as:
Wietrzyk, J., Nevozhay, D., Milczarek, M. et al. Cancer Chemother Pharmacol (2008) 62: 787. doi:10.1007/s00280-007-0666-6

Abstract

Purpose

Active and less toxic vitamin D analogs could be useful for clinical applications. In the present study, we evaluated the toxicity and antitumor effect of two new synthetic analogs of vitamin D, namely PRI-1906 [(24E)-24a-Homo-(1S)-1,25-dihydroxyergocalciferol] and its side-chain unsaturated homo analog PRI-1907.

Methods

The toxicity and calcemic activity, as well as antitumor effect of calcitriol analogs was investigated in vivo. The studies were performed in a mouse mammary 16/C cancer model. Since calcitriol and its analogs inhibited 16/C tumor growth only slightly, we applied them in the combined therapy with cyclophosphamide (CY). Moreover, cell cycle analysis and VDR and p27 expression were investigated.

Results

The LD50 values after five daily subcutaneous (s.c.) injections were 7.8, 10.0 and 2.4 μg/kg per day for calcitriol, PRI-1906 and PRI-1907, respectively. The serum calcium level increased to 40, 23 and 63% over the control for these compounds. We also compare the antitumor activity of the PRI-1906 with the calcitriol and previously studied PRI-2191 (1,24-dihydroxyvitamin D3, tacalcitol). Statistically significant inhibition of tumor growth by calcitriol up to the eighth day was observed in all schedules applied. PRI-1906 inhibited the tumor growth at doses 1 and 5 μg/kg per day, and PRI-2191 only at the dose 5 μg/kg per day.

Conclusion

Addition of vitamin D analogs increased the antitumor effect of CY. PRI-1906 exhibited toxicity higher than PRI-2191 but lower than calcitriol and antitumor activity similar to both PRI-2191 and calcitriol. This new analog seems to be a good candidate for the combined treatment of mammary cancer.

Keywords

Steroid Calcitriol (1S,24R)-1,24-dihydroxyvitamin D3 Chemotherapy Antitumor Analogs 

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Joanna Wietrzyk
    • 1
  • Dmitry Nevozhay
    • 1
    • 2
  • Magdalena Milczarek
    • 1
  • Beata Filip
    • 1
  • Andrzej Kutner
    • 3
  1. 1.Department of Experimental OncologyInstitute of Immunology and Experimental TherapyWroclawPoland
  2. 2.Kopvillem Institute of Medical PhysicsVladivostokRussia
  3. 3.Pharmaceutical Research InstituteWarsawPoland

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