MNU-induced mammary gland carcinogenesis: Chemopreventive and therapeutic effects of vitamin D and Seocalcitol on selected regulatory vitamin D receptor pathways

The effects of administration of vitamin D3 and Seocalcitol on MNU-induced carcinogenesis of mammary gland in Sprague-Dawley rats have been investigated. Administration of both substances in a weekly dose of 7 μg/kg caused prolonged latency of mammary gland tumors. The latency of tumors was markedly prolonged for 30–40 days by Seocalcitol. Using PET analysis, reduction in [18F]2-fluoro-2-deoxy-d-glucose (FDG) uptake or tumor volume in tumors chemopreventively treated with vitamin D3 were detected in MNU-induced tumors, vitamin D3 reduced expression of 25-hydroxylase (25OHase) (p < 0.01) and 24-hydroxylase (24OHase) (p < 0.01) and Seocalcitol 24OHase. Positive regulation of 25OHase mRNA level after the treatment with vitamin D3 was observed in liver, while in kidney, vitamin D3 and Seocalcitol induced expression of 24OHase was significant. Our observations indicate a cross talk between respective pathways of VDR, RARs/RXRs, TRs and ERs in carcinogenesis process.

► Vitamin D3 and Seocalcitol as tools in prevention and therapy of mammary gland cancer. ► Seocalcitol markedly prolongs tumor latency. ► MicroPET analysis confirms tumor reduction after treatment with vitamin D3. ► Vitamin D3 or Seocalcitol reduce vitamin D3 metabolism in tumor tissue. ► Crosstalk within nuclear receptor regulatory pathways.