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Vitamin D/Ca 2+ ‐dependent calpain and caspases: novel molecular targets for obesity‐related breast cancer drug discovery (261.5)
Author(s) -
Sergeev Igor
Publication year - 2014
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.28.1_supplement.261.5
Subject(s) - apoptosis , vitamin d and neurology , adipose tissue , calpain , endocrinology , medicine , chemistry , breast cancer , cancer , cancer research , caspase , programmed cell death , biochemistry , enzyme
Removal of breast cancer cells (BCC) via apoptosis results in a decrease in tumor size. Induction of apoptosis in adipocytes decreases adiposity due to long‐term reduction in adipose tissue mass. The hormone 1,25(OH) 2 ‐vitamin D 3 (1,25D) triggers apoptosis in both BCC and mature adipocytes via apoptotic Ca 2+ signal ‒ a sustained increase in intracellular Ca 2+ . This signal acts as an initiator of apoptosis that directly recruits Ca 2+ ‐dependent apoptotic effectors, calpain and caspase‐12, in BCC and adipocytes. Normal mammary epithelial cells are resistant to Ca 2+ ‐mediated apoptosis because Ca 2+ regulatory mechanisms in these cells do not support the apoptosis‐inducing Ca 2+ signal. Remarkably, high vitamin D and Ca intakes activate Ca 2+ ‐mediated apoptotic pathway in adipose tissue and decrease body and fat weight gain in obese mice. Induction of apoptosis with 1,25D in adipocytes, particularly in the tumor‐surrounding adipose tissue involved in tumor progression, contributes to anticancer effects of the hormone. The 1,25D ‒ Ca 2+ link between breast cancer and obesity supports rationale to include the vitamin D/Ca 2+ ‐dependent apoptotic proteases as molecular targets for discovery of new therapeutic and preventive agents for breast cancer and obesity as well as to consider increasing vitamin D and Ca intakes as a promising approach to protecting against breast cancer and decreasing adiposity. Supported by USDA 2009‐35200‐05008 and SD00H325. Grant Funding Source : Supported by USDA