Vitamin D and cancer: a review of molecular mechanisms

Fleet, James C.; DeSmet, Marsha; Johnson, Robert L.; Li, Yan

doi:10.1042/bj20110744

Cited by 346 publications

(310 citation statements)

References 206 publications

(236 reference statements)

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“…4 Autophagy, which is a specific type of programmed cell death, is closely associated with, and shares some molecular events and regulators with, apoptosis. 5 Recent evidence suggests a strong link between autophagy and SCI.…”

Section: Introductionmentioning

confidence: 99%

Effects of calcitriol on experimental spinal cord injury in rats

Jin

et al. 2016

Spinal Cord

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Study design: Experimental, controlled, animal study. Objectives: To evaluate the effects of calcitriol on oxidative stress, apoptosis, autophagy and locomotor recovery in rats after spinal cord injury (SCI). Setting: China. Methods: Ninety female rats were randomly divided into three groups. Laminectomy only was performed in the control group. The SCI group received laminectomy as well as spinal cord compression injury. In the calcitriol group, SCI rats received an intraperitoneal injection of calcitriol (2 μg kg − 1 day − 1 ). Oxidative stress was assessed by the tissue superoxide dismutase (SOD) activity and the contents of glutathione (GSH) and malondialdehyde (MDA). The extent of apoptosis was assessed by immunohistochemistry for C-caspase3, TUNEL staining and western blotting for C-caspase3, Bax and Bcl2. Transmission electron microscopy was used to examine autophagosomes in the injured spinal cord of calcitriol-treated rats. Autophagy was detected by western blotting for LC3-II, Beclin1 and p62. Histological changes were assessed by haematoxylin and eosin staining and Nissl staining. Functional recovery was reflected by the Basso, Beattie and Bresnahan locomotion rating scale and the inclined plane test. Results: With calcitriol treatment, oxidative stress was decreased, SOD activity and GSH content were increased and MDA content was decreased. Moreover, apoptosis was inhibited in the SCI plus calcitriol group. However, a higher level of autophagy was detected in the lesions of the calcitriol group compared with the SCI group. Histological damage and neuron loss after SCI were reduced in calcitrioltreated rats, and functional recovery was significantly promoted in the calcitriol group compared with controls. Conclusions: Calcitriol promotes locomotor recovery after SCI by reducing oxidative stress and inhibiting apoptosis, as well as promoting autophagy.

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Section: Introductionmentioning

confidence: 99%

Effects of calcitriol on experimental spinal cord injury in rats

Jin

et al. 2016

Spinal Cord

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“…8 Vitamin D3 is transported in the circulation by the DBP (vitamin D binding protein). 9 Once delivered to the liver, vitamin D is hydroxylated on its side chain to form 25OHD. The kidney is the primary site where the active form of vitamin D, 1,25(OH) 2 D (VD3), is produced.…”

Section: Introductionmentioning

confidence: 99%

“…10 VD3 has been shown to induce the expression of several enzymes involved in the antioxidant defence system. 9 There is also some evidence that VD3 regulates the genes for proteins that protect the genome. 9 Little information is available for the antioxidant property of VD3.…”

Section: Introductionmentioning

confidence: 99%

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Protective Effect of Melatonin and 1,25-Dihydroxyvitamin D3 on Renal Ischemia–Reperfusion Injury in Rats

et al. 2013

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Ischemia-reperfusion (I/R) injury induces the generation of reactive oxygen species (ROS) which affect many organs. This study was designed to investigate the roles of melatonin and 1,25-dihydroxyvitamin D 3 (VD3) on renal I/R injury. Thirty male Wistar albino rats were divided into five groups: group 1, control; group 2, right nephrectomy (RN) þ I/R in the contralateral kidney; group 3, melatonin þ RN þ I/R; group 4, VD 3 þ RN þ I/R; and group 5, melatonin þ VD 3 þ RN þ I/R. Melatonin (10 mg/kg), VD3 (0.5 μg/kg), and melatonin plus VD3 were injected intraperitoneally for 7 days before renal I/R. After 7 days, right nephrectomy was initially performed and left renal artery was clamped for 45 min. After 45-min reperfusion, the serum and kidney tissue samples were obtained for assays. Melatonin and VD3 had an ameliorative effect on biochemical parameters such as serum creatinine (SCr) and blood urea nitrogen (BUN). Renal tissue malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO) levels, and superoxide dismutase (SOD) activity were determined. Renal I/R decreased the kidney tissue GSH levels and SOD activity and increased the NO levels as compared with control group. However, melatonin and VD3 and melatonin plus VD3 treatment significantly increased the tissue GSH levels and SOD activity and decreased the NO levels compared with those of I/R group. Meanwhile, MDA levels were not different between the control and I/R groups. But, MDA levels decreased in all treated groups compared to I/R and control groups. These data support that melatonin and VD3 have beneficial effects on renal injury.

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“…Due to factors such as reduced intake, absorption, and decreased exposure to sunlight, aging adults (≥50 y of age) are especially susceptible (3)(4)(5)(6). Notably, this predisposition for lower 25OHD levels in the elderly has been linked to higher risk for numerous age-related disorders, including cancer and metabolic and vascular diseases (7)(8)(9)(10).…”

mentioning

confidence: 99%

Vitamin D prevents cognitive decline and enhances hippocampal synaptic function in aging rats

Latimer¹,

Brewer²,

Searcy³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

180

103

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Vitamin D is an important calcium-regulating hormone with diverse functions in numerous tissues, including the brain. Increasing evidence suggests that vitamin D may play a role in maintaining cognitive function and that vitamin D deficiency may accelerate agerelated cognitive decline. Using aging rodents, we attempted to model the range of human serum vitamin D levels, from deficient to sufficient, to test whether vitamin D could preserve or improve cognitive function with aging. For 5-6 mo, middle-aged F344 rats were fed diets containing low, medium (typical amount), or high (100, 1,000, or 10,000 international units/kg diet, respectively) vitamin D3, and hippocampal-dependent learning and memory were then tested in the Morris water maze. Rats on high vitamin D achieved the highest blood levels (in the sufficient range) and significantly outperformed low and medium groups on maze reversal, a particularly challenging task that detects more subtle changes in memory. In addition to calcium-related processes, hippocampal gene expression microarrays identified pathways pertaining to synaptic transmission, cell communication, and G protein function as being up-regulated with high vitamin D. Basal synaptic transmission also was enhanced, corroborating observed effects on gene expression and learning and memory. Our studies demonstrate a causal relationship between vitamin D status and cognitive function, and they suggest that vitamin D-mediated changes in hippocampal gene expression may improve the likelihood of successful brain aging.V itamin D, a secosteroid hormone known for its role in bone and calcium homeostasis, is now well recognized for its many diverse functions and actions on a variety of tissues and cell types (1, 2). Vitamin D typically refers to the precursor forms of the hormone obtained through the skin's exposure to sunlight [vitamin D3 (VitD3)] or from dietary sources (VitD3 or VitD2). A metabolite of vitamin D, 25-hydroxyvitamin D (25OHD), is a serum biomarker of vitamin D status or repletion. In recent years, there is particular concern that large segments of the population may have low levels of 25OHD, and therefore are vitamin D-deficient (3). Due to factors such as reduced intake, absorption, and decreased exposure to sunlight, aging adults (≥50 y of age) are especially susceptible (3-6). Notably, this predisposition for lower 25OHD levels in the elderly has been linked to higher risk for numerous age-related disorders, including cancer and metabolic and vascular diseases (7-10).Inadequate vitamin D status also correlates with a greater risk for cognitive decline in the elderly (4,(11)(12)(13)(14)(15), suggesting that optimal levels may promote healthy brain aging (16,17). Because the brain expresses vitamin D receptors (VDRs) and can synthesize the active form of the hormone, the possible cognitive enhancing effects of vitamin D may reflect a primary action in the brain rather than a result of secondary systemic effects (18)(19)(20)(21)(22). Indeed, we and others have shown that vitamin D, as ...

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Vitamin D and cancer: a review of molecular mechanisms

Cited by 346 publications

References 206 publications

Effects of calcitriol on experimental spinal cord injury in rats

Effects of calcitriol on experimental spinal cord injury in rats

Protective Effect of Melatonin and 1,25-Dihydroxyvitamin D3 on Renal Ischemia–Reperfusion Injury in Rats

Vitamin D prevents cognitive decline and enhances hippocampal synaptic function in aging rats

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