TY - JOUR T1 - Vitamin D and Cellular Ca<sup>2+</sup> Signaling in Breast Cancer JF - Anticancer Research JO - Anticancer Res SP - 299 LP - 302 VL - 32 IS - 1 AU - IGOR N. SERGEEV Y1 - 2012/01/01 UR - http://ar.iiarjournals.org/content/32/1/299.abstract N2 - The hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) regulates a variety of signaling pathways via intracellular Ca2+. Modulation of apoptosis is emerging as a promising strategy for treatment and prevention of cancer. Cellular Ca2+ has been implicated in triggering of apoptosis, however, the vitamin D/Ca2+-dependent targets involved in apoptotic signaling have not been identified. Here, we review our studies on mechanisms of 1,25(OH)2D3-induced Ca2+ signaling and Ca2+-mediated apoptosis in breast cancer cells. The results obtained demonstrate that 1,25(OH)2D3 regulates Ca2+ entry from the extracellular space, Ca2+ mobilization from the intracellular stores and intracellular Ca2+ buffering. In breast cancer cells, 1,25(OH)2D3 induces the apoptotic Ca2+ signal, a sustained increase in concentration of intracellular Ca2+ ([Ca2+]i) reaching elevated, but not cytotoxic levels. This increase in [Ca2+]i is associated with activation of Ca2+-dependent μ-calpain and Ca2+/calpain-dependent caspase-12. Activation of these proteases appears to be sufficient for the execution of apoptosis in cancer cells. Normal mammary epithelial cells resist induction of apoptosis with 1,25(OH)2D3 due to their large Ca2+-buffering capacity. The results indicate that the 1,25(OH)2D3-induced cellular Ca2+ signal can act as an apoptotic initiator that directly recruits Ca2+-dependent apoptotic effectors capable of executing apoptosis. These findings provide a novel rationale for evaluating the role of vitamin D in prevention and treatment of breast cancer. ER -