The new insight on the regulatory role of the vitamin D3 in metabolic pathways characteristic for cancerogenesis and neurodegenerative diseases

Kubis-Kubiak, Adriana; Piwowar, Agnieszka

doi:10.1016/j.arr.2015.07.008

Cited by 22 publications

(15 citation statements)

References 164 publications

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“…Thus, the choice of a single target against the complex and poorly understood pathophysiology of PD has been shown inefficient [4], what guides the search for new drugs with pleotropic properties, as vitamin D (VD3). Appropriate levels of VD3, whose active metabolite is 1α,25-dihydroxy-vitamin D or simply calcitriol, are essential for the normal neuronal function, such as immunomodulation and detoxification processes [5]. VD3 shows a potent antioxidant activity, being able to reduce lipid peroxidation and to improve brain enzyme activity.…”

Section: Introductionmentioning

confidence: 99%

Vitamin D protects dopaminergic neurons against neuroinflammation and oxidative stress in hemiparkinsonian rats

Lima

Lopes

Costa

et al. 2018

J Neuroinflammation

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BackgroundThe deficiency in 1α, 25-dihydroxyvitamin D3 (VD3) seems to increase the risk for neurodegenerative pathologies, including Parkinson’s disease (PD). The majority of its actions are mediated by the transcription factor, VD3 receptor (VD3R).MethodsThe neuroprotective effects of VD3 were investigated on a PD model. Male Wistar rats were divided into the following groups: sham-operated (SO), 6-OHDA-lesioned (non-treated), and 6-OHDA-lesioned and treated with VD3 (7 days before the lesion, pre-treatment or for 14 days after the 6-OHDA striatal lesion, post-treatment). Afterwards, the animals were subjected to behavioral tests and euthanized for striatal neurochemical and immunohistochemical assays. The data were analyzed by ANOVA and the Tukey test and considered significant for p < 0.05.ResultsWe showed that pre- or post-treatments with VD3 reversed behavioral changes and improved the decreased DA contents of the 6-OHDA group. In addition, VD3 reduced the oxidative stress, increased (TH and DAT), and reduced (TNF-alpha) immunostainings in the lesioned striata. While significant decreases in VD3R immunoreactivity were observed after the 6-OHDA lesion, these changes were blocked after VD3 pre- or post-treatments. We showed that VD3 offers neuroprotection, decreasing behavioral changes, DA depletion, and oxidative stress. In addition, it reverses partially or completely TH, DAT, TNF-alpha, and VD3R decreases of immunoreactivities in the non-treated 6-OHDA group.ConclusionsTaken together, VD3 effects could result from its anti-inflammatory and antioxidant actions and from its actions on VD3R. These findings should stimulate translational research towards the VD3 potential for prevention or treatment of neurodegenerative diseases, as PD.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1266-6) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Vitamin D protects dopaminergic neurons against neuroinflammation and oxidative stress in hemiparkinsonian rats

Lima

Lopes

Costa

et al. 2018

J Neuroinflammation

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“…It should be emphasized, however, that the role of activated cholecalciferol is much more diverse. The non-calcemic effects of vitamin D include regulation of proliferation, differentiation and apoptosis [ 19 , 20 , 21 , 22 , 23 , 24 ], and 1,25(OH) 2 D is one of the most potent inhibitors of cell growth [ 25 , 26 ]. Therefore, vitamin D analogs are considered as promising anticancer compounds, which is supported by data from preclinical studies and epidemiological that relate low levels of vitamin D to an increased risk of cancer [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ].…”

Section: Introductionmentioning

confidence: 99%

Antiproliferative Activity of Double Point Modified Analogs of 1,25-Dihydroxyvitamin D2 Against Human Malignant Melanoma Cell Lines

Piotrowska

Wierzbicka

Nadkarni

et al. 2016

IJMS

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Vitamin D is a lipid soluble steroid hormone with pleiotropic biological properties, including regulation of cell proliferation, differentiation and apoptosis. As to these desirable anticancer actions, 1,25-dihydroxyvitamins D and analogs have been reported to inhibit the proliferation and to induce differentiation of a wide variety of cancer cell types, including human malignant melanoma. However, there is a need for novel and more efficacious vitamin D analogs, and how best to design such is still an open issue. A series of double point modified (DPM) analogs of 1,25-dihydroxyvitamin D2 (1,25(OH)2D2) induced differentiation of the vitamin D receptor (VDR) positive A375 and VDR negative SK-MEL 188b human malignant melanoma cell lines. Surprisingly, the dose of 1,25(OH)2D2 required to inhibit the proliferation of the A375 melanoma cell line by was several fold lower than that required in the case of 1,25(OH)2D3. To evaluate the impact of the modification in the side chain (additional 22-hydroxyl) and in the A-ring (5,6-trans modification), the regular side-chain of vitamin D2 or D3 was retained in the structure of our analogs. As expected, 5,6-trans modification was advantageous to enhancing the anti-proliferative activity of analogs, but not as a single point modification (SPM). Very unexpectedly, the additional 22-hydroxyl in the side-chain reduced significantly the anti-proliferative activity of both the natural and 5,6-trans series analogs. Finally, an induction of pigmentation in melanoma SK-MEL 188b cells was observed to sensitized cells to the effect of vitamin D analogs.

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“…Many authors have reported a protective role of endogenous vitamin D status in cancer diseases. 9,10 The protective effect of vitamin D is explained by two cellular…”

Section: Introductionmentioning

confidence: 99%

Association of the vitamin D receptorFokIgene polymorphism with sex- and non-sex-associated cancers: A meta-analysis

et al. 2017

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Currently higher morbidity and mortality rates are observed in cancer diseases, especially sex-dependent cancers. A positive role of endogenous vitamin D concentration in cancer diseases has been reported in many publications. Furthermore, there has been observed a relationship between serum vitamin D and testosterone concentrations in an elderly Caucasian population carrying the vitamin D receptor FokI gene polymorphism. The aim of this study was to investigate whether the vitamin D receptor FokI polymorphism is associated with cancerogenesis in sex-dependent cancers. The MEDLINE and ResearchGate databases were used to search for articles up to January 2017, and 96 articles concerning the FokI polymorphism were chosen. Odds ratios with 95% confidence intervals were used to assess the strength of associations between polymorphisms of vitamin D receptor and cancer risk in the described populations. The fixed-effects model and the DerSimonian-Laird random-effects model (with weights based on the inverse variance) were used to calculate summary odds ratios, and both within- and between-study variation were considered. Generally, the F variant reduces the risk of cancer by 4% (odds ratio = 0.96, p value = 0.0057). This effect is particularly evident in female sex-associated cancers (odds ratio = 0.96, 95% confidence interval: 0.93-0.99, p value = 0.0259), but it is not observed in non-sex-associated cancers. Polymorphism FokI is associated with breast and ovarian cancers.

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The new insight on the regulatory role of the vitamin D3 in metabolic pathways characteristic for cancerogenesis and neurodegenerative diseases

Cited by 22 publications

References 164 publications

Vitamin D protects dopaminergic neurons against neuroinflammation and oxidative stress in hemiparkinsonian rats

Vitamin D protects dopaminergic neurons against neuroinflammation and oxidative stress in hemiparkinsonian rats

Antiproliferative Activity of Double Point Modified Analogs of 1,25-Dihydroxyvitamin D2 Against Human Malignant Melanoma Cell Lines

Association of the vitamin D receptorFokIgene polymorphism with sex- and non-sex-associated cancers: A meta-analysis

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