Vitamin D-mediated apoptosis in cancer and obesity

Abstract

Low vitamin D status has been associated with increased risk of several cancers and obesity; concurrently, obesity and cancer have been linked to impaired vitamin D status. In both cancer and obesity, selective elimination of cancer cells and adipocytes can result in decreasing tumor size and a long-term reduction in adipose tissue mass. These effects can be achieved through induction of apoptotic cell death. -dependent apoptotic proteases as promising targets for discovery of new therapeutic and preventive agents for cancer and obesity. The concept of maintaining an increased vitamin D status for protecting against cancer and decreasing adiposity also warrants further evaluation.

High vitamin D and calcium intakes increase bone mineral (Ca and P) content in high-fat diet-induced obese mice

“…It should be cautioned that animal studies on the role of vitamin D and calcium in obesity often have not been confirmed in the observational human studies and that the intervention clinical trials are limited (see Song and Sergeev [25] for a review). Moreover, vitamin D status can serve as an excellent marker of good health, and many of the variables that contribute to low vitamin D status (unhealthy dietary pattern, physical inactivity, aging, skin pigmentation) are also risk factors for the development of obesity and bone disorders [30].…”

“…Particularly, low calcium intake and a low vitamin D status are associated with an increased risk of secondary hyperparathyroidism, osteopenia, and bone fractures, whereas high calcium and high vitamin D intakes are considered as protective factors against osteoporosis [21][22][23][24][25]. Importantly, obesity is often associated with low concentration of circulating 25-hydroxyvitamin D (25[OH]D) and low calcium intake [25][26][27][28], and increased dietary calcium and vitamin D intakes can reduce body weight gain and weight and percentage of body fat in diet-induced obesity (DIO) [25,[29][30][31][32]. Therefore, it is plausible that obesity accompanied by a low 25(OH)D concentration and a low calcium intake can have detrimental effects on bone health.…”

1α,25(OH) 2D3 Sensitive Cytosolic pH Regulation and Glycolytic Flux in Human Endometrial Ishikawa Cells

“…1,25(OH) 2 D 3 has been shown to stimulate apoptosis of diverse tumor cells [3, 4]. The effect has been attributed in part to sustained increase of cytosolic Ca 2+ activity [47]. The present observation point to 1,25(OH) 2 D 3 sensitivity of the serine/threonine protein kinase AKT which supports cell survival and affects a variety of cellular processes including proliferation, survival, and protein translation [48].…”

Regulation of apoptosis in adipocytes and breast cancer cells by 1,25-dihydroxyvitamin D3: a link between obesity and breast cancer

“…We [9,10,12,24,26,40,41] and others [42,43] have demonstrated that 1,25(OH) 2 D 3 induces apoptosis in cancer cells and adipocytes and that apoptosis induced by 1,25(OH) 2 D 3 in these cells depends on Ca 2+ signaling [8,9,12,23]. The efficacy of vitamin D analogues in cancer does not always correlate with their binding affinity to nVDRs, and not all cancer cell lines expressing nVDRs respond to 1,25(OH) 2 D 3 .…”

“…However, mechanisms control ling adipocyte apoptosis are not known and the ability of adipocytes to undergo apoptosis has not even been conclusively demonstrated. We [10,40,41] have shown that 1,25(OH) 2 D 3 induces apoptosis in mature mouse 3T3L1 adipocytes via the activation of the Ca 2+ dependent calpain and Ca 2+ /calpaindependent caspase 12. Treat ment of adipocytes with 1,25(OH) 2 D 3 induced, in a concen tration and timedependent fashion, a sustained increase in the basal level of intracellular Ca 2+ .…”