Vitamin D and cancer

• Published in: The Journal of nutritional biochemistry Vol. 13; no. 5; pp. 252 - 264
• Main Authors: Mehta, Rajendra G., Mehta, Rajeshwari R.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.05.2002; Elsevier Science
• Subjects: Analogs of vitamin D; Antineoplastic agents; Biological and medical sciences; Carcinogenesis; Carcinogenesis, carcinogens and anticarcinogens; Chemotherapy; Foods and miscellaneous; Mechanism of action; Medical sciences; Metabolism; Pharmacology. Drug treatments; Tumors; VDR; Vitamin D; Vitamin D; Metabolism; Mechanism of action; VDR; Carcinogenesis; Analogs of vitamin D; Human; Steroid hormone; Review; Anticarcinogen; Biological activity; Feeding; Micronutrient; Treatment; Diet; Analog; Animal; Biological receptor
• DOI: 10.1016/S0955-2863(02)00183-3
• ISSN: 0955-2863

Vitamin D, a steroid hormone and exerts its biological effects through its active metabolite 1α, 25 dihydroxyvitamin D3 [1,25(OH)2D3]. Like steroid hormones, 1,25(OH)2D3 is efficacious at very low concentrations and serves as a ligand for vitamin D receptors (VDR), associating with VDR very high affinity. Despite its potent property as a differentiating agent, its use in the clinical practice is hampered by the induction of hypercalcemia at a concentration required to suppress cancer cell proliferation. Therefore nearly 400 structural analogs of vitamin D3 have been synthesized and evaluated for their efficacy and toxicity. Among these analogs, relatively less toxic but highly efficacious analogs, EB1089, RO24-5531, 1α-hydroxyvitamin D5 and a few others have been evaluated in a preclinical toxicity and in Phase I clinical trials for dose tolerance in advanced cancer patients. Clinical trials using vitamin D analogs for prevention or therapy of cancer patients are still in their infancy. Vitamin D mediates its action by two independent pathways. Genomic pathway involves nuclear VDR and induces biological effects by interactions with hormone response elements and modulation of differential gene expressions. Evidence also suggests that vitamin D analogs also interact with steroid hormone(s) inducible genes. The non-genomic pathway is characterized by rapid actions of vitamin D. It involves interactions with membrane-VDR interactions and its interactions with protein kinase C and by altering intracellular calcium channels. Thus, the development of nontoxic analogs of vitamin D analogs and understanding of their molecular mechanism(s) of action are of significant importance in the prevention and treatment of cancer by vitamin D.