Abstract

The active form of vitamin D₃, 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃), is mostly known for its importance in the maintenance of calcium and phosphate homeostasis. However, next to its classical effects on bone, kidney and intestine, 1,25(OH)₂D₃ also exerts antineoplastic effects on various types of cancer. The use of 1,25(OH)₂D₃ itself as treatment against neoplasia is hampered by its calcemic side effects. Therefore, 1,25(OH)₂D₃-derived analogs were developed that are characterized by lower calcemic side effects and stronger antineoplastic effects. This review mainly focuses on the role of 1,25(OH)₂D₃ in breast, prostate and colorectal cancer (CRC) and the underlying signaling pathways. 1,25(OH)₂D₃ and its analogs inhibit proliferation, angiogenesis, migration/invasion and induce differentiation and apoptosis in malignant cell lines. Moreover, prostaglandin synthesis and Wnt/b-catenin signaling are also influenced by 1,25(OH)₂D₃ and its analogs. Human studies indicate an inverse association between serum 25(OH)D₃ values and the incidence of certain cancer types. Given the literature, it appears that the epidemiological link between vitamin D₃ and cancer is the strongest for CRC, however more intervention studies and randomized placebo-controlled trials are needed to unravel the beneficial dose of 1,25(OH)₂D₃ and its analogs to induce antineoplastic effects.