Vitamin D and Intracellular Calcium

Сергеев, И. Н.; Rhoten, William B.; Спиричев, В. Б.

doi:10.1007/978-1-4899-1789-8_12

Cited by 22 publications

(39 citation statements)

References 115 publications

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“…Induction of apoptotic cell death is emerging as a promising strategy for chemoprevention and treatment of breast cancer, because it may allow for selective elimination of cancer cells [10 -12]. Our findings [10,13] suggest that regulation of apoptosis in normal and cancer human mammary epithelial cells by the key cellular signal, Ca 2+ , is different. Therefore, plant bioactive compounds (e. g. PMFs) that trigger Ca 2+ -mediated apoptosis in cancer cells, but not normal cells, would be of tremendous importance for breast cancer prevention and treatment.…”

Section: Introductionmentioning

confidence: 57%

Apoptosis‐inducing activity of hydroxylated polymethoxyflavones and polymethoxyflavones from orange peel in human breast cancer cells

Сергеев¹,

et al. 2007

Molecular Nutrition Food Res

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Sweet orange (Citrus sinensis L.) peel is a rich resource of flavonoids, especially polymethoxyflavones (PMFs). Citrus flavonoids exert a broad spectrum of biological activity, including antiproliferative and proapoptotic effects in cancer cells. We have recently shown that individual PMFs from orange peel induce Ca(2+)-mediated apoptosis in human breast cancer cells and that hydroxylation of PMFs is critical for enhancing their proapoptotic activity. Here, we report that the fraction of orange peel extract containing a mixture of non-hydroxylated PMFs (75.1%) and hydroxylated PMFs (5.44%) and the fraction containing only hydroxylated PMFs (97.2%) induce apoptosis in those cells as well. Treatment of MCF-7 breast cancer cells with these fractions inhibited growth and induced apoptosis associated with an increase in the basal level of intracellular Ca(2+). Effective concentrations of the hydroxylated PMFs fraction in inhibiting growth, inducing apoptosis, and increasing intracellular Ca(2+) were lower than those of the non-hydroxylated PMFs fraction. Our results strongly imply that bioactive PMFs from orange peel exert proapoptotic activity in human breast cancer cells, which depends on their ability to induce an increase in intracellular Ca(2+ )and thus, activate Ca(2+)-dependent apoptotic proteases.

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Section: Introductionmentioning

confidence: 57%

Apoptosis‐inducing activity of hydroxylated polymethoxyflavones and polymethoxyflavones from orange peel in human breast cancer cells

Сергеев¹,

et al. 2007

Molecular Nutrition Food Res

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“…The ER may participate in the initiation of apoptosis by at least two different mechanisms, i.e. Ca 2ϩ signaling and unfolded protein re- sponse (14,46 release to occur in breast cancer cells (12,13,47). Furthermore, the kinetics of Ca 2ϩ release correlated well with the onset of apoptosis suggesting that Ca 2ϩ may play a direct role in the apoptosis induction.…”

Section: Discussionmentioning

confidence: 96%

Calcium and Calpain as Key Mediators of Apoptosis-like Death Induced by Vitamin D Compounds in Breast Cancer Cells

Mathiasen¹,

Сергеев²,

Bastholm³

et al. 2002

Journal of Biological Chemistry

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199

167

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Very little is known about the signaling pathways mediating vitamin D-induced cell death. A single family of proteases, the caspases, has until recently been considered the pivotal executioner of all programmed cell death (8). Therefore it is interesting to note that breast cancer cells treated with vitamin D compounds die in the complete absence of effector caspase activation (4). Despite the lack of the caspase activation, dying cells present several characteristics of apoptosis, i.e. rounding, shrinkage, and detachment of cells as well as DNA strand breaks and DNA fragmentation (4, 9, 10). Furthermore, antiapoptotic proteins Bcl-2 and Bcl-X L can rescue breast cancer cells from death induced by the active form of vitamin D or its analogs (4). This apoptosis-like death program appears also independent of cysteine cathepsins and p53 tumor suppressor protein (4, 11). Instead, the elevation in the intracellular free calcium ([Ca 2ϩ ] i ) brought about by vitamin D compounds correlates with the induction of apoptosis in breast cancer cells (9,12,13).Data from studies employing various pharmaceutical modulators of calcium homeostasis have suggested that the elevation in [Ca 2ϩ ] i is a sufficient signal to induce apoptosis in several model systems, even though it may also have the opposite effect in other systems (14). Further supporting the idea that the elevation in [Ca 2ϩ ] i may mediate apoptosis, studies based on modulated expression of calcium-binding proteins, calbindin-D 28k or glucose-regulated proteins GRP78 and GRP94, have shown that Ca 2ϩ buffering can confer protection against various apoptotic stimuli (15-19). The calcium-dependent neutral cysteine proteases, calpains, are frequently activated in apoptosis models involving elevated [Ca 2ϩ ] i (20 -22). Two forms of calpains, -calpain and m-calpain or type I and type II calpain, respectively, are ubiquitously expressed in human cells (23)(24)(25). The active forms of the enzymes consist of a variable large subunit (80 kDa) and a common small subunit (30 kDa). To become active, calpains require an elevation in [Ca 2ϩ ] i , and the autoproteolytic cleavage of the enzymes further enhances their activity. Whereas m-calpain requires Ca 2ϩ at a millimolar range, micromolar concentrations are enough for the activation of -calpain (in vitro; lower in cells). So far no difference in the substrate specificity of the two isozymes has been found. Growing evidence suggests that calpains may play a central role in the execution of apoptosis either upstream or * This work was supported by the Danish Medical Research Council, the Danish Cancer Society (to I. S. M. and M. J.), and by Grant CA67317 from the NCI, National Institutes of Health (to I. N. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. § Present address: Molecular Biology, Novo Nordisk A/S, Bagsvaerd DK 2880, Denmar...

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“…The genomic responses utilise signal-transduction pathways linked to the nuclear/cytosolic VDR, while the rapid responses utilise signal-transduction pathways linked to the membrane VDR localised in the plasma and, possibly, endoplasmic reticulum membranes (58) as well as to the plasma membrane-associated rapid response steroid hormone-binding protein (59,60) . Nuclear and membrane VDR have been demonstrated in many (over forty) tissues, including adipose tissue (21,53,61) . In these target tissues, the VDR functions both as a transcriptional factor to influence more than 3% of the human genome and a modulator of a number of cellular signal-transduction pathways, including Ca 2þ signalling.…”

Section: Vitamin D As a Hormonal And Cellular Regulatormentioning

confidence: 99%

“…Elevated levels of calbindins dramatically increase the cytosolic Ca 2þ -buffering capacity and an increase in Ca -mediated apoptosis (65,67,69,117) . We have shown (21,22,65) that a sustained (not reaching cytotoxic levels) increase in intracellular Ca 2þ concentration signals the cell to enter the apoptotic pathway via activation of the Ca 2þ -dependent protease m-calpain followed by activation of the Ca 2þ /calpain-dependent release from the endoplasmic reticulum stores through the inositol 1,4,5-trisphosphate and ryanodine receptors (21,22,56,65,117) . Importantly, we have also shown that 1,25(OH) 2 D 3 induces apoptosis in adipocytes (23,58) and that apoptosis induced by 1,25(OH) 2 D 3 in these cells depends on Ca 2þ signalling (22,24,117) .…”

Section: Calcium Intake and Faecal Fat Excretionmentioning

confidence: 99%

Calcium and vitamin D in obesity

Song

Сергеев

2012

Nutr. Res. Rev.

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New and more effective nutritional measures are urgently needed for the prevention of obesity. The role of Ca and vitamin D in obesity has been recently implicated. Low Ca intake and low vitamin D status have been linked with an increased risk of obesity in epidemiological studies; however, clinical intervention trials designed to test this association have produced controversial results. The suggested anti-obesity mechanisms of Ca and vitamin D include the regulation of adipocyte death (apoptosis), adipogenesis and lipid metabolism. Dietary Ca has been also shown to increase faecal fat excretion. The potential role of Ca and vitamin D in shifting energy balance towards a more negative state is an area of considerable interest. Ultimately, a review of recent research findings does not allow the reaching of a definitive conclusion that increasing Ca intake and rising vitamin D status will influence fat mass and body weight or decrease the risk of obesity and overweight.

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Vitamin D and Intracellular Calcium

Cited by 22 publications

References 115 publications

Apoptosis‐inducing activity of hydroxylated polymethoxyflavones and polymethoxyflavones from orange peel in human breast cancer cells

Apoptosis‐inducing activity of hydroxylated polymethoxyflavones and polymethoxyflavones from orange peel in human breast cancer cells

Calcium and Calpain as Key Mediators of Apoptosis-like Death Induced by Vitamin D Compounds in Breast Cancer Cells

Calcium and vitamin D in obesity

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