Exploring Vitamin D Metabolism and Function in Cancer

Exp Mol Med. 2018 Apr 16;50(4):20. doi: 10.1038/s12276-018-0038-9.

Abstract

Vitamin D, traditionally known as an essential nutrient, is a precursor of a potent steroid hormone that regulates a broad spectrum of physiological processes. In addition to its classical roles in bone metabolism, epidemiological, preclinical, and cellular research during the last decades, it revealed that vitamin D may play a key role in the prevention and treatment of many extra-skeletal diseases such as cancer. Vitamin D, as a prohormone, undergoes two-step metabolism in liver and kidney to produce a biologically active metabolite, calcitriol, which binds to the vitamin D receptor (VDR) for the regulation of expression of diverse genes. In addition, recent studies have revealed that vitamin D can also be metabolized and activated through a CYP11A1-driven non-canonical metabolic pathway. Numerous anticancer properties of vitamin D have been proposed, with diverse effects on cancer development and progression. However, accumulating data suggest that the metabolism and functions of vitamin D are dysregulated in many types of cancer, conferring resistance to the antitumorigenic effects of vitamin D and thereby contributing to the development and progression of cancer. Thus, understanding dysregulated vitamin D metabolism and function in cancer will be critical for the development of promising new strategies for successful vitamin D-based cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Gene Expression Regulation, Neoplastic / drug effects
  • Hormones / metabolism
  • Humans
  • Metabolic Networks and Pathways / drug effects
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Receptors, Calcitriol / metabolism
  • Vitamin D / metabolism*
  • Vitamin D / pharmacology
  • Vitamin D / therapeutic use

Substances

  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Antioxidants
  • Hormones
  • Receptors, Calcitriol
  • Vitamin D