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

Abstract
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.
AuthorsDana Macejová, Slavomíra Ondková, Lucia Jakubíková, Alžbeta Mlynarčíková, Soňa Scsuková, Ján Liška, Július Brtko
JournalToxicology letters (Toxicol Lett) Vol. 207 Issue 1 Pg. 60-72 (Nov 10 2011) ISSN: 1879-3169 [Electronic] Netherlands
PMID21843606 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Chemical References
  • RNA, Messenger
  • Receptors, Calcitriol
  • Cholecalciferol
  • Methylnitrosourea
  • Mixed Function Oxygenases
  • Calcitriol
  • seocalcitol
Topics
  • Animals
  • Calcitriol (analogs & derivatives, pharmacology)
  • Cell Transformation, Neoplastic (chemically induced, drug effects)
  • Cholecalciferol (pharmacology)
  • Female
  • Histocytochemistry
  • Mammary Neoplasms, Experimental (chemically induced, enzymology, metabolism, prevention & control)
  • Methylnitrosourea (toxicity)
  • Mixed Function Oxygenases (genetics, metabolism)
  • Positron-Emission Tomography
  • RNA, Messenger (chemistry, genetics)
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Calcitriol (genetics, metabolism)
  • Reverse Transcriptase Polymerase Chain Reaction

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