Mechanisms of the anti-cancer and anti-inflammatory actions of vitamin D

Annu Rev Pharmacol Toxicol. 2011;51:311-36. doi: 10.1146/annurev-pharmtox-010510-100611.

Abstract

Calcitriol, the hormonally active form of vitamin D, is being evaluated in clinical trials as an anti-cancer agent. Calcitriol exerts multiple anti-proliferative, pro-apoptotic, and pro-differentiating actions on various malignant cells and retards tumor growth in animal models of cancer. Calcitriol also exhibits several anti-inflammatory effects including suppression of prostaglandin (PG) action, inhibition of p38 stress kinase signaling, and the subsequent production of pro-inflammatory cytokines and inhibition of NF-κB signaling. Calcitriol also decreases the expression of aromatase, the enzyme that catalyzes estrogen synthesis in breast cancer, both by a direct transcriptional repression and indirectly by reducing PGs, which are major stimulators of aromatase transcription. Other important effects include the suppression of tumor angiogenesis, invasion, and metastasis. These calcitriol actions provide a basis for its potential use in cancer therapy and chemoprevention. We summarize the status of trials involving calcitriol and its analogs, used alone or in combination with known anti-cancer agents.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Anticarcinogenic Agents / pharmacology
  • Anticarcinogenic Agents / therapeutic use
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Calcitriol / pharmacology*
  • Calcitriol / therapeutic use
  • Disease Models, Animal
  • Humans
  • Inflammation / drug therapy
  • Inflammation / physiopathology
  • Neoplasms / drug therapy
  • Neoplasms / physiopathology
  • Neoplasms / prevention & control

Substances

  • Anti-Inflammatory Agents
  • Anticarcinogenic Agents
  • Antineoplastic Agents
  • Calcitriol