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Vitamin D/calcium‐mediated apoptosis in cancer cells and adipocytes
Author(s) -
Sergeev Igor N
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.917.16
Subject(s) - apoptosis , microbiology and biotechnology , extracellular , calcium signaling , cancer cell , intracellular , chemistry , calpain , signal transduction , vitamin d and neurology , biology , cancer , endocrinology , biochemistry , genetics , enzyme
1,25(OH) 2 D 3 (1,25D) regulates variety of signaling pathways via intracellular Ca 2+ . Modulating apoptosis is emerging as a strategy for treatment and prevention of cancer and obesity. Cellular Ca 2+ has been implicated in triggering apoptosis, however vitamin D/Ca 2+ ‐dependent targets involved in apoptotic signaling have not been identified. We investigated mechanisms of 1,25D‐induced Ca 2+ signaling and Ca 2+ ‐mediated apoptosis in cancer cells and adipocytes. The results obtained demonstrate that 1,25D regulates Ca 2+ entry from the extracellular space, Ca 2+ mobilization from intracellular stores and intracellular Ca 2+ buffering. We have also shown that that the apoptotic Ca 2+ signal represents a sustained increase in [Ca 2+ ] i reaching elevated, but not cytotoxic levels. The apoptotic Ca 2+ signal induced by 1,25D in breast cancer cells and mature adipocytes is associated with activation of Ca 2+ ‐dependent μ‐calpain and Ca 2+ /calpain‐dependent caspase‐12. Activation of these proteases appears to be sufficient for execution of apoptosis. Normal mammary epithelial cells are resistant to induction of apoptosis with 1,25D due to their large Ca 2+ buffering capacity. These results indicate that 1,25D‐induced cellular Ca 2+ signal can act as an apoptotic initiator that directly recruits Ca 2+ ‐dependent apoptotic effectors capable of executing apoptosis. Supported by USDA 2009‐35200‐05008 and SD00H325.