The role of vitamin D in cancer prevention and treatment.
Calcitriol (1,25-dihydroxyvitamin D(3)), the hormonally active form of vitamin D, exerts growth inhibitory and prodifferentiating effects on many malignant cells and retards tumor growth in animal models. Calcitriol is being evaluated as an anticancer agent in several human cancers. The mechanisms underlying the anticancer effects of calcitriol include inhibition of cell proliferation, stimulation of apoptosis, suppression of inflammation, and inhibition of tumor angiogenesis, invasion, and metastasis. This review discusses some of the molecular pathways mediating these anticancer actions of calcitriol and the preclinical data in cell culture and animal models. The clinical trials evaluating the use of calcitriol and its analogues in the treatment of patients with cancer are described. The reasons for the lack of impressive beneficial effects in clinical trials compared with the substantial efficacy seen in preclinical models are discussed.
Krishnan
Aruna V
AV
Department of Medicine, Division of Endocrinology, Stanford University School of Medicine, Stanford, CA 94305-5103, USA.
Trump
Donald L
DL
Johnson
Candace S
CS
Feldman
David
D
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002117:Calcitriol / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D054637:Dual-Specificity Phosphatases / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000517:prevention & control; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D011453:Prostaglandins / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood / Q000627:therapeutic use* / Q000633:toxicity
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D016328:NF-kappa B; D011453:Prostaglandins; D014807:Vitamin D; C120407:DUSP10 protein, human; D054639:Mitogen-Activated Protein Kinase Phosphatases; D054637:Dual-Specificity Phosphatases; D002117:Calcitriol