Novel Mediators of Vitamin D Signaling in Cancer and Obesity

Author(s): Igor N. Sergeev.

Journal Name: Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Under Re-organization)

Volume 9 , Issue 3 , 2009

Abstract:

The hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) regulates a variety of signaling pathways in health and disease via intracellular Ca2+. An emerging approach in treatment and prevention of cancer and obesity is induction of apoptotic cell death. Cellular Ca2+ signals have been implicated in triggering apoptosis, however vitamin D/Ca2+-dependent mediators involved in apoptotic signaling have not been identified. Our studies reviewed here demonstrate that 1,25(OH)2D3 induces Ca2+-mediated apoptotic death of cancer cells and adipocytes via activation of the novel targets, Ca2+-dependent μ-calpain and Ca2+/calpain-dependent caspase-12. In this pathway -- sustained increase in intracellular Ca2+ → μ-calpain activation → caspase-12 activation → apoptosis -- cellular Ca2+ acts as an apoptotic initiator and directly recruits Ca2+-dependent apoptotic effectors capable of executing apoptosis. Our findings provide a new rationale for evaluating the role of vitamin D in prevention and treatment of cancer and obesity.

Keywords: 1,25-dihydroxyvitamin D3, vitamin D, intracellular Ca2+, calcium, apoptosis, calpain, caspase-12, adipocytes, breast cancer, obesity

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Article Details

VOLUME: 9
ISSUE: 3
Year: 2009
Page: [153 - 158]
Pages: 6
DOI: 10.2174/187152209789760521
Price: $58

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