Protection against cyclophosphamide-induced alopecia and inhibition of mammary tumor growth by topical 1,25-dihydroxyvitamin D3 in mice

Int J Cancer. 1998 Jan 19;75(2):303-9. doi: 10.1002/(sici)1097-0215(19980119)75:2<303::aid-ijc21>3.0.co;2-c.

Abstract

Twenty-one-day-old BALB/c mice were shaved on the back to synchronize hair growth. On day 30 or 31, when at least 90% of mice exhibited hair regrowth in the shaved area, 1,25(OH)2D3 was applied topically to the shaved area daily for 5 days. On the 6th day, cyclophosphamide (Cytoxan, CTX) was injected i.p. to induce hair loss in the shaved area. Alopecia was induced in a dose-dependent manner by CTX treatment within 1 to 2 weeks. This effect was reduced significantly if mice were pre-treated with 1,25(OH)2D3, though only slight protection was observed in female mice. Interestingly, this 1,25(OH)2D3-mediated protection against hair loss was attenuated in male mice but became more significant in female mice when they were inoculated with the EMT-6 murine mammary tumor prior to treatment. More importantly, topical treatment with 1,25(OH)2D3 alone was able to inhibit EMT-6 tumor growth in both male and female BALB/c mice. Furthermore, 1,25(OH)2D3 pre-treatment also augmented the anti-tumor effect of CTX. Our results demonstrate that topical application of 1,25(OH)2D3 can protect against CTX-induced alopecia both in tumor-free and in tumor-bearing mice in a sex-dependent manner. Moreover, 1,25(OH)2D3 was shown, either alone or in combination with CTX, to inhibit tumor growth.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Topical
  • Alopecia / prevention & control*
  • Animals
  • Antineoplastic Agents, Alkylating / adverse effects*
  • Calcitriol / administration & dosage*
  • Cell Division / drug effects
  • Cyclophosphamide / adverse effects*
  • Female
  • Male
  • Mammary Neoplasms, Experimental / drug therapy*
  • Mice
  • Mice, Inbred BALB C

Substances

  • Antineoplastic Agents, Alkylating
  • Cyclophosphamide
  • Calcitriol