Regulation of extrarenal vitamin D metabolism as a tool for colon and prostate cancer prevention

Recent Results Cancer Res. 2003;164:413-25. doi: 10.1007/978-3-642-55580-0_30.

Abstract

Though 1,25-dihydroxyvitamin D3 (1,25-D3) as well as some vitamin D analogs have an antimitotic as well as a differentiating action, therapeutic application in tumor patients is still precluded due to their hypercalcemic action at the necessary concentration. Our observation that early during progression, colon tumor cells express CYP27B1, the enzyme essential for 1,25-D3 synthesis, as well as the vitamin D receptor (VDR) at a higher level than normal colon cells led to the speculation that, by induction of this expression, a physiological defense against tumor progression could be activated and enhanced. In some Asian countries where soy products are a main staple, prostate and breast tumor incidence is extremely low. We speculated that this could be due to regulation of CYP enzymes by phytoestrogens present in soy such as genistein. In prostate tumor cells, the 1,25-dihydroxyvitamin D3 catabolizing enzyme CYP24 is frequently highly expressed. We were able to demonstrate that genistein down-regulates expression of CYP24 to almost nil, which would result in enhancement of local 1,25-D3 levels and improved mitotic control of tumor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / metabolism*
  • Colon / drug effects
  • Colon / metabolism*
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / enzymology
  • Colonic Neoplasms / prevention & control*
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism*
  • Dietary Proteins / administration & dosage
  • Estrogens, Non-Steroidal / pharmacology
  • Gene Expression / drug effects
  • Genistein / chemistry
  • Humans
  • Isoflavones / pharmacology
  • Male
  • Phytoestrogens
  • Plant Preparations / pharmacology
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / prevention & control*
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Soybean Proteins / administration & dosage
  • Soybean Proteins / chemistry
  • Steroid Hydroxylases / genetics
  • Steroid Hydroxylases / metabolism*
  • Vitamin D / metabolism*
  • Vitamin D3 24-Hydroxylase

Substances

  • Dietary Proteins
  • Estrogens, Non-Steroidal
  • Isoflavones
  • Phytoestrogens
  • Plant Preparations
  • RNA, Messenger
  • Soybean Proteins
  • Vitamin D
  • Cytochrome P-450 Enzyme System
  • Genistein
  • Steroid Hydroxylases
  • Vitamin D3 24-Hydroxylase
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase