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

► Vitamin D 3 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 D 3. ► Vitamin D 3 or Seocalcitol reduce vitamin D 3 metabolism in tumor tissue. ► Crosstalk within nuclear receptor regulatory pathways. The effects of administration of vitamin D 3 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 D 3 were detected in MNU-induced tumors, vitamin D 3 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 D 3 was observed in liver, while in kidney, vitamin D 3 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.