Calcitroic Acid–A Review

Yu, Olivia B.; Arnold, Leggy A.

doi:10.1021/acschembio.6b00569

Cited by 30 publications

(18 citation statements)

References 60 publications

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“…In addition, 1,25(OH) 2 D 3 can be generated locally in many cell types (keratinocytes, dendritic cells, melanocytes, lymphocytes and cancer cells) expressing appropriate enzymatic machinery [ 6 , 7 ]. The level of 1,25(OH) 2 D 3 and its metabolites in circulation are tightly regulated through a negative feedback loop by 24-hydroxylase (CYP24A1), which metabolizes calcitriol into water-soluble and inactive calcitroic acid [ 8 ]. The catalytically inactive splicing variant of CYP24A1 ( CYP24SV ) may serve as dominant negative regulator of vitamin D 3 catabolism and possibly contribute to the extracellular accumulation of 1,25(OH)2D 3 [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Antiproliferative Activity of Non-Calcemic Vitamin D Analogs on Human Melanoma Lines in Relation to VDR and PDIA3 Receptors

Wasiewicz

Piotrowska

Wierzbicka

et al. 2018

IJMS

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Vitamin D is a precursor for secosteroidal hormones, which demonstrate pleiotropic biological activities, including the regulation of growth and the differentiation of normal and malignant cells. Our previous studies have indicated that the inhibition of melanoma proliferation by a short side-chain, low calcemic analog of vitamin D—21(OH)pD is not fully dependent on the expression of vitamin D receptor (VDR). We have examined the effects of classic vitamin D metabolites, 1,25(OH)2D3 and 25(OH)D3, and two low calcemic vitamin D analogs, (21(OH)pD and calcipotriol), on proliferation, mRNA expression and vitamin D receptor (VDR) translocation in three human melanoma cell lines: WM98, A375 and SK-MEL-188b (subline b of SK-MEL-188, which lost responsiveness to 1,25(OH)2D3 and became VDR−/−CYP27B1−/−). All tested compounds efficiently inhibited the proliferation of WM98 and A375 melanoma cells except SK-MEL-188b, in which only the short side-chain vitamin D analog—21(OH)pD was effective. Overall, 21(OH)pD was the most potent compound in all three melanoma cell lines in the study. The lack of responsiveness of SK-MEL-188b to 1,25(OH)2D3, 25(OH)D3 and calcipotriol is explained by a lack of characteristic transcripts for the VDR, its splicing variants as well as for vitamin D-activating enzyme CYP27B1. On the other hand, the expression of VDR and its splicing variants and other vitamin D related genes (RXR, PDIA3, CYP3A4, CYP2R1, CYP27B1, CYP24A1 and CYP11A1) was detected in WM98 and A375 melanomas with the transcript levels being modulated by vitamin D analogs. The expression of VDR isoforms in WM98 cells was stimulated strongly by calcipotriol. The antiproliferative activities of 21(OH)pD appear not to require VDR translocation to the nucleus, which explains the high efficacy of this noncalcemic pregnacalciferol analog in SK-MEL-188b melanoma, that is, VDR−/−. Therefore, we propose that 21(OH)pD is a good candidate for melanoma therapy, although the mechanism of its action remains to be defined.

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Section: Introductionmentioning

confidence: 99%

Antiproliferative Activity of Non-Calcemic Vitamin D Analogs on Human Melanoma Lines in Relation to VDR and PDIA3 Receptors

Wasiewicz

Piotrowska

Wierzbicka

et al. 2018

IJMS

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“…Synthesis of calcitroic acid through the 24‐oxidation pathway has been described in bone cells and the kidney suggesting a rapid clearance mechanism of 1,25(OH) 2 D3 in these sites . Calcitroic acid has binding affinity for the vitamin D receptor isolated from chick intestines and vitamin D binding protein in rat serum . Conjugation of calcitroic acid can occur by glucuronidation, sulfation, amino acid, and glutathione conjugation and methylation.…”

Section: Cyp24a1 and Vitamin D Catabolismmentioning

confidence: 99%

“…63 Calcitroic acid has binding affinity for the vitamin D receptor isolated from chick intestines and vitamin D binding protein in rat serum. 66,67 Conjugation of calcitroic acid can occur by glucuronidation, sulfation, amino acid, and glutathione conjugation and methylation. Conjugation in kidney leads to excretion; however, the conjugated form in the liver can lead to intestinal secretion and de-conjugation, which can also occur with other vitamin D metabolites.…”

Section: Metabolism To Active Vitamin Dmentioning

confidence: 99%

“…Conjugation in kidney leads to excretion; however, the conjugated form in the liver can lead to intestinal secretion and de-conjugation, which can also occur with other vitamin D metabolites. 66,67 The 23-hydroxylation pathway involves the conversion of 1α,25(OH) 2 D3 to 1α,25R(OH) 2 D3-26,23S-lactone through sequential oxidations. Initially, 1,25(OH) 2 D3 is hydroxylated at C23 to form 1α,23S,25(OH) 3 D3.…”

Section: Metabolism To Active Vitamin Dmentioning

confidence: 99%

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The vitamin D metabolome: An update on analysis and function

Jenkinson

2019

Cell Biochemistry & Function

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Current understanding of vitamin D tends to be focussed on the measurement of the major circulating form 25‐hydroxyvitamin D3 (25OHD3) and its conversion to the active hormonal form, 1α,25‐dihydroxyvitamin D3 (1α,25(OH)2D3) via the enzyme 25‐hydroxyvitamin D‐1α‐hydroxylase (CYP27B1). However, whilst these metabolites form the endocrine backbone of vitamin D physiology, it is important to recognise that there are other metabolic and catabolic pathways that are now recognised as being crucially important to vitamin D function. These pathways include C3‐epimerization, CYP24A1 hydroxylase, CYP11A1 alternative metabolism of vitamin D3, and phase II metabolism. Endogenous metabolites beyond 25OHD3 are usually present at low endogenous levels and may only be functional in specific target tissues rather than in the general circulation. However, the technologies available to measure these metabolites have also improved, so that measurement of alternative vitamin D metabolic pathways may become more routine in the near future. The aim of this review is to provide a comprehensive overview of the various pathways of vitamin D metabolism, as well as describe the analytical techniques currently available to measure these vitamin D metabolites.

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“…There is a bewildering array of unknowns. For example, because clinical medicine has had little interest in excreted metabolites of vitamin D, considerable uncertainty exists with humans as to whether calcitroic acid is primarily excreted via the bile or also via urine—or both ( Horst et al, 2005 ; Reddy and Tserng, 1989 ; Yu and Arnold, 2016 ); if it is excreted extensively via the feces, it is unknown how quickly or extensively it would desorb from fecal material into the aqueous phase of sewage. All told, calcitroic acid would not seem to serve as a stoichiometric proxy for biologically active vitamin D status, especially because of continual regulatory shifts in the network of pathways.…”

Section: Considerations For New Potential Bioscim Biomarkersmentioning

confidence: 99%

Monitoring wastewater for assessing community health: Sewage Chemical-Information Mining (SCIM)

Daughton

2018

Science of The Total Environment

158

118

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Timely assessment of the aggregate health of small-area human populations is essential for guiding the optimal investment of resources needed for preventing, avoiding, controlling, or mitigating human exposure risks, as well as for maintaining or promoting health. Seeking those interventions yielding the greatest benefit with respect to the allocation of resources is critical for making progress toward community sustainability, reducing health disparities, promoting social justice, and maintaining or improving collective health and well-being. More informative, faster, and less-costly approaches are needed for guiding investigation of cause-effect linkages involving communities and stressors originating from both the built and natural environments. One such emerging approach involves the continuous monitoring of sewage for chemicals that serve as indicators of the collective status of human health (or stress/disease) or any other facet relevant to gauging time-trends in community-wide health. This nascent approach can be referred to as Sewage Chemical-Information Mining (SCIM) and involves the monitoring of sewage for the information that resides in the form of natural and anthropogenic chemicals that enter sewers as a result of the everyday actions, activities, and behaviors of humans. Of particular interest is a specific embodiment of SCIM that would entail the targeted monitoring of a broad suite of endogenous biomarkers of key physiologic processes (as opposed to xenobiotics or their metabolites). This application is termed BioSCIM—an approach roughly analogous to a hypothetical community-wide collective clinical urinalysis, or to a hypothetical en masse human biomonitoring program. BioSCIM would be used for gauging the status or time-trends in community-wide health on a continuous basis. This paper presents an update on the progress made with the development of the BioSCIM concept in the period of time since its original publication in 2012, as well as the next steps required for its continued development.

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Calcitroic Acid–A Review

Cited by 30 publications

References 60 publications

Antiproliferative Activity of Non-Calcemic Vitamin D Analogs on Human Melanoma Lines in Relation to VDR and PDIA3 Receptors

Antiproliferative Activity of Non-Calcemic Vitamin D Analogs on Human Melanoma Lines in Relation to VDR and PDIA3 Receptors

The vitamin D metabolome: An update on analysis and function

Monitoring wastewater for assessing community health: Sewage Chemical-Information Mining (SCIM)

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