ArticleScientific reports2025
1,24,25(OH)
Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
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Authors and funding
7 authors.
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Abstract
1,24,25-trihydroxyvitamin D3 (1,24,25(OH)3D3), a primary catabolite of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), exhibits biological activity including antitumor effects but has less calcemic activity than 1,25(OH)2D3. In the present work, we investigated the biological and genomic effects of 1,24,25(OH)3D3 in human primary epidermal keratinocytes (HPEKp), which are not only essential for vitamin D3 photoproduction and activation but also serve as a direct target for 1,25(OH)2D3 via its nuclear receptor, the VDR. Although 1,24,25(OH)3D3 is a metabolite of the CYP24A1-catalyzed deactivation pathway, it showed comparable antiproliferative and VDR-nuclear translocation efficiency to 1,25(OH)2D3. Transcriptomic profiling revealed a substantial overlap in differentially expressed genes (DEGs) between both secosteroids, with up to 70% similarity, but also highlighted distinct gene regulation patterns, some specific for 1,24,25(OH)3D3 and others for 1,25(OH)2D3. Functional enrichment analyses confirmed shared modulation of immune signaling, keratinocyte differentiation, and GPCR-related (G protein-coupled receptor) pathways, with unique activation of processes such as gastrulation and cornified envelope formation by 1,24,25(OH)3D3. Moreover, both compounds preserved normal expression patterns of several genes associated with development of head and neck squamous cell carcinoma, confirming their anti-cancer potential. Considering its broad biological activity and the lower calcemic effect of 1,24,25(OH)3D3 compared to 1,25(OH)2D3, it appears to be a potential candidate for further clinical studies. It should be noted that both 1,25(OH)2D3 and 1,24,25(OH)3D3 were used at a supraphysiological concentration of 100 nM to ensure detectable effects in vitro; therefore, our results require further confirmation, including in vivo studies.
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