ArticlePloS one2010
Products of vitamin D3 or 7-dehydrocholesterol metabolism by cytochrome P450scc show anti-leukemia effects, having low or absent calcemic activity.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
112 citing papers in PubMed, 149 citations in OpenAlex.
- Can Current Recommendations on Sun Exposure Sufficiently Increase Serum Vitamin D Level?: One-Month Randomized Clinical Trial.Journal of Korean medical science · 2020Trial
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- Anticancer Activity of Vitamin D, Lumisterol and Selected Derivatives against Human Malignant Melanoma Cell Lines.International journal of molecular sciences · 2024Article
- Biological Effects of CYP11A1-Derived Vitamin D and Lumisterol Metabolites in the Skin.The Journal of investigative dermatology · 2024Review
- Beneficial Impact of Inhaled 25(OH)-Vitamin D3 and 1,25(OH)2-Vitamin D3 on Pulmonary Response in the Murine Model of Hypersensitivity Pneumonitis.International journal of molecular sciences · 2024Article
- Review
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- Is There a Role of Vitamin D in Alzheimer's Disease?CNS & neurological disorders drug targets · 2024Review
- Urinary Metabolomic Analysis of Prostate Cancer by UPLC-FTMS and UPLC-Ion Trap MSDiagnostics (Basel, Switzerland) · 2023Article
- Vitamin D in Neurological Diseases.International journal of molecular sciences · 2022Review
- Nongenomic Activities of Vitamin D.Nutrients · 2022Review
- Novel CYP11A1-Derived Vitamin D and Lumisterol Biometabolites for the Management of COVID-19.Nutrients · 2022Review
- Vitamin D3 and Ischemic Stroke: A Narrative Review.Antioxidants (Basel, Switzerland) · 2022Review
- Vitamin D Signaling in Psoriasis: Pathogenesis and Therapy.International journal of molecular sciences · 2022Review
- Metabolic activation of tachysterolFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- CYP11A1‑derived vitamin D hydroxyderivatives as candidates for therapy of basal and squamous cell carcinomas.International journal of oncology · 2022Article
- The Multiple Effects of Vitamin D against Chronic Diseases: From Reduction of Lipid Peroxidation to Updated Evidence from Clinical Studies.Antioxidants (Basel, Switzerland) · 2022Review
- Synthesis of Deuterium-Labeled Vitamin D Metabolites as Internal Standards for LC-MS Analysis.Molecules (Basel, Switzerland) · 2022Article
52 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 7 institutions in 3 countries.
Funding
Abstract
backgroundCytochrome P450scc metabolizes vitamin D3 to 20-hydroxyvitamin D3 (20(OH)D3) and 20,23(OH)(2)D3, as well as 1-hydroxyvitamin D3 to 1alpha,20-dihydroxyvitamin D3 (1,20(OH)(2)D3). It also cleaves the side chain of 7-dehydrocholesterol producing 7-dehydropregnenolone (7DHP), which can be transformed to 20(OH)7DHP. UVB induces transformation of the steroidal 5,7-dienes to pregnacalciferol (pD) and a lumisterol-like compounds (pL). METHODS AND
findingsTo define the biological significance of these P450scc-initiated pathways, we tested the effects of their 5,7-diene precursors and secosteroidal products on leukemia cell differentiation and proliferation in comparison to 1alpha,25-dihydroxyvitamin D3 (1,25(OH)(2)D3). These secosteroids inhibited proliferation and induced erythroid differentiation of K562 human chronic myeloid and MEL mouse leukemia cells with 20(OH)D3 and 20,23(OH)(2)D3 being either equipotent or slightly less potent than 1,25(OH)(2)D3, while 1,20(OH)(2)D3, pD and pL compounds were slightly or moderately less potent. The compounds also inhibited proliferation and induced monocytic differentiation of HL-60 promyelocytic and U937 promonocytic human leukemia cells. Among them 1,25(OH)(2)D3 was the most potent, 20(OH)D3, 20,23(OH)(2)D3 and 1,20(OH)(2)D3 were less active, and pD and pL compounds were the least potent. Since it had been previously proven that secosteroids without the side chain (pD) have no effect on systemic calcium levels we performed additional testing in rats and found that 20(OH)D3 had no calcemic activity at concentration as high as 1 microg/kg, whereas, 1,20(OH)(2)D3 was slightly to moderately calcemic and 1,25(OH)(2)D3 had strong calcemic activity.
conclusionsWe identified novel secosteroids that are excellent candidates for anti-leukemia therapy with 20(OH)D3 deserving special attention because of its relatively high potency and lack of calcemic activity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.