Abstract 6831: Systems biology analysis of vitamin D3 reveals new anticancer properties
Bibliographic record
Abstract
Abstract Introduction: Vitamin D3 (also known as cholecalciferol) is an essential nutrient and hormone that is obtained through both sunlight-mediated cutaneous synthesis and direct dietary intake. Vitamin D3 functions to inhibit tumor cell growth by arresting the cell cycle at G0/G1 phases, increasing apoptosis, and reducing nuclear β-catenin levels to prevent the formation of cancer-promoting T-cell factor complexes. This study identified the cancer cell lines most responsive to in vitro treatment with vitamin D3, as well as the compounds and genetic perturbations that are most similar to treatment with vitamin D3. Methods: For cell line response analyses, the NCI60 dataset from the US National Cancer Institute was used. Human cancer cell lines were incubated for 24 hours and treated with cholecalciferol for 48 hours at 5 different ten-fold serial dilution concentrations. Sulforhodamine B was used to measure cell survival. To identify genetic and compound perturbations similar to vitamin D3, data was obtained from the L1000 gene expression assay and CLUE. In this assay, mRNA transcript abundance was measured in 978 human landmark genes and inferred for over 11, 000 others to compare gene expression levels to those induced by vitamin D3. Results: The least sensitive cell line to vitamin D3 was the multiple myeloma cell line RPMI-8226 (IC50=56.3 µM), and the most sensitive was the colorectal cancer cell line HCT-116 (IC50 = 18.2 µM). Overall, vitamin D3 was most potent against lymphoid, renal, and melanoma cancer cell lines, and least potent against myeloma cell lines. As indicated by high median tau scores, administration of vitamin D3 induced gene expression changes similar to OTX2 and ZNF114 knockdowns; OTX2 is a transcription factor associated with neurological organ development while ZNF114 is a zinc-finger protein important for transcription regulation, and both have a biological network connection to vitamin D3. Vitamin D3 treatment has similar genetic effects to known therapeutic compounds like VX-702, nelfinavir, and calcipotriol. Conclusions: This study provides a comprehensive in vitro examination of the cancer cell lines most impacted by treatment with vitamin D3. Further research will help better inform the use of vitamin D3 in nutrition plans and guide its use in cancer prevention and treatment. Citation Format: Ashiana M. Sunderji, Shivangi Roy, Adin Aggarwal, Kenneth W. Yip. Systems biology analysis of vitamin D3 reveals new anticancer properties [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6831.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".