Antiproliferative effects of 1,25-dihydroxyvitamin D3 on breast cells: a mini review

• Published in: Brazilian journal of medical and biological research 2002-01, Vol.35 (1), p.1-9
• Main Authors: Bortman, P, Folgueira, M A A K, Katayama, M L H, Snitcovsky, I M L, Brentani, M M
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - pharmacology; BIOLOGY; Breast Neoplasms - blood; Breast Neoplasms - pathology; Breast tumor; Calcitriol; Calcitriol - blood; Calcitriol - pharmacology; Calcitriol analog; Calcitriol receptor; Cell Division - drug effects; Cell proliferation; Cell Transformation, Neoplastic - drug effects; Female; Humans; MEDICINE, RESEARCH & EXPERIMENTAL; Receptors, Calcitriol - blood
• ISSN: 0100-879X; 1414-431X; 0100-879X; 1414-431X
• DOI: 10.1590/s0100-879x2002000100001

The hormone 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3), the active form of vitamin D3, is an important regulator of calcium homeostasis, exerts antiproliferative effects on various cell systems and can induce differentiation in some kinds of hematopoietic cells. These effects are triggered by its receptor, vitamin D receptor (VDR), a phosphoprotein member of the nuclear receptor superfamily, which functions as a transcriptional factor. VDR binds as a heterodimer with retinoid X receptor (R X R) to hexameric repeats, characterized as vitamin D-responsive elements present in the regulatory region of target genes such as osteocalcin, osteopontin, calbindin-D28K, calbindin-D9K, p21WAF1/CIP1, TGF-beta2 and vitamin D 24-hydroxylase. Many factors such as glucocorticoids, estrogens, retinoids, proliferation rate and cell transformation can modulate VDR levels. VDR is expressed in mammary tissue and breast cancer cells, which are potential targets to hormone action. Besides having antiproliferative properties, vitamin D might also reduce the invasiveness of cancer cells and act as an anti-angiogenesis agent. All of these antitumoral features suggest that the properties of vitamin D could be explored for chemopreventive and therapeutic purposes in cancer. However, hypercalcemia is an undesirable side effect associated with pharmacological doses of 1,25-(OH)2D3. Some promising 1,25-(OH)2D3 analogs have been developed, which are less hypercalcemic in spite of being potent antiproliferative agents. They represent a new field of investigation.