Evidence map›Paper›PMID 40146328›Full record

ArticleMedical oncology (Northwood, London, England)2025

Vitamin D3 and its active form calcitriol suppress erythroleukemia through upregulation of CHAC1 and downregulation of NOTCH1.

Jiankun Hong, Zhongyou Yang, Jian Gao, Kunlin Yu, Anling Hu, Yi Kuang, Babu Gajendran, Eldad Zacksenhaus, Xiao Xiao, Chunlin Wang and 2 more

Abstract read
PubMed Publisher
In one paragraph

Article in Medical oncology (Northwood, London, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Jiankun Hong *State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang, 550014, China.
Zhongyou Yang *Natural Products Research Center of Guizhou Province, Province Science City, No. 3491 Bai-Jin Avenue, High Tech Zone, Baiyun District, Guiyang, 550014, China.
Jian GaoState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang, 550014, China.
Kunlin YuState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang, 550014, China.
Anling HuState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang, 550014, China.
Yi KuangState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang, 550014, China.
Babu GajendranSchool of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, 550025, Guizhou, China.
Eldad ZacksenhausDivision of Advanced Diagnostics, Toronto General Research Institute, University Health Network, Toronto, ON, Canada.
Xiao XiaoState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang, 550014, China.
Chunlin WangState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang, 550014, China. wangchunlin3323@163.com.ORCID http://orcid.org/0000-0003-1889-5685
Wuling LiuState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang, 550014, China. emmalao@163.com.ORCID http://orcid.org/0000-0001-7344-5754
Yaacov Ben-DavidState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang, 550014, China. yaacovbendavid@hotmail.com.ORCID http://orcid.org/0000-0002-9020-6074

Funding

Guizhou Administration of Traditional Chinese Medicine QZYY-2024-023Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences Research Grant GZCNP202203Zresearch grants from the National Natural Science Foundation of China 21867009Science and Technology Department of Guizhou Province grants QKHJC-ZK [2022] YB297Science and Technology Department of Guizhou Province grants QKHJC-ZK [2023] YB240Science and Technology Department of Guizhou Province grants QKHJC-ZK[2024] YB 641science and technology development youth grant of the Education Department of Guizhou Province Qianjiaoji [2024] 97
6 · The paper itself

Abstract

Vitamin D3 (VD3) and its active form calcitriol (Ca) exhibit anti-neoplastic activity against several types of cancer, although the underlying mechanism is not fully understood. Herein, we tested the effects of VD3 and Ca on erythro-leukemogenesis and investigated the underlying mechanism. VD3 and Ca treatment strongly inhibited cancer progression in a mouse model of erythroleukemia induced by the Friend virus. In tissue culture, VD3 and Ca inhibited proliferation of leukemic cell lines. Growth inhibition was associated with induction of G1 phase cell cycle arrest and apoptosis. Transcription of the VD3 receptor, VDR, is strongly induced by Ca, but not VDR. However, leukemia growth suppression by both VD3 and Ca is shown to be independent of VDR. In leukemic cells, both VD3 and Ca induced genes associated with metabolic pathways. Both VD3 and Ca induce the cytosolic glutathione degradase CHAC1 through activation of the ER stress response pathway ATF3/ATF4/CHOP genes. Higher expression of CHAC1 also suppressed the oncogene NOTCH1. Accordingly, knockdown of CHAC1 antagonized the inhibitory effect of VD3 and Ca on leukemic growth leading to higher NOTCH1 expression. Conversely, overexpression of CHAC1 suppressed leukemia cell growth and inhibited the expression of NOTCH1. Additionally, glutathione antagonized leukemia cell suppression induced by VD3 and Ca, demonstrating that this vitamin inhibits the proliferation of leukemic cells via CHAC1. Taken together, our results demonstrated that VD3 and Ca can prolong the survival of leukemia mice and inhibit the proliferation of erythroleukemia cell HEL through CHAC1 or CHAC1-mediated NOTCH1 inhibition.

Indexed as

CalcitriolCholecalciferolLeukemia, Erythroblastic, AcuteReceptor, Notch1AnimalsApoptosisCell Line, TumorCell ProliferationDown-RegulationHumansMiceUp-RegulationCalcitriolCholecalciferolNOTCH1 protein, humanReceptor, Notch1CalcitriolCHAC1Leukemia progressionNOTCH1VD3

Identifiers

PMID40146328

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 Socratic graph.