Evidence map›Paper›PMID 32898337›Full record

ArticleClinical and translational medicine2020

Natural HDAC-1/8 inhibitor baicalein exerts therapeutic effect in CBF-AML.

Xiaoxuan Yu, Hui Li, Po Hu, Yingjie Qing, Xiangyuan Wang, Mengyuan Zhu, Hongzheng Wang, Zhanyu Wang, Jingyan Xu, Qinglong Guo and 1 more

Open access · goldAbstract read
In one paragraph

Article in Clinical and translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 10% of its field
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

24 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.

  1. Pooled it
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  11. Natural medicinal compounds target signal transduction pathways to overcome ABC drug efflux transporter-mediated multidrug resistance in cancer.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2023
    Review
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  15. Review
  16. Article
  17. Review
  18. Review
  19. Review
  20. Molecular Assessment ofEvidence-based complementary and alternative medicine : eCAM · 2022
    Article
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

11 authors at 3 institutions in 1 country.

Xiaoxuan YuState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, China Pharmaceutical University, Nanjing, Jiangsu, China.
Hui LiState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, China Pharmaceutical University, Nanjing, Jiangsu, China.
Po HuState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, China Pharmaceutical University, Nanjing, Jiangsu, China.
Yingjie QingState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, China Pharmaceutical University, Nanjing, Jiangsu, China.
Xiangyuan WangState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, China Pharmaceutical University, Nanjing, Jiangsu, China.
Mengyuan ZhuState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, China Pharmaceutical University, Nanjing, Jiangsu, China.
Hongzheng WangState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, China Pharmaceutical University, Nanjing, Jiangsu, China.
Zhanyu WangState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, China Pharmaceutical University, Nanjing, Jiangsu, China.
Jingyan XuDepartment of Hematology, The Affiliated DrumTower Hospital of Nanjing University Medical School, Nanjing, China.
Qinglong GuoState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, China Pharmaceutical University, Nanjing, Jiangsu, China.ORCID https://orcid.org/0000-0001-5165-2592
Hui HuiState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, China Pharmaceutical University, Nanjing, Jiangsu, China.
China Pharmaceutical University · CNNanjing Drum Tower Hospital · CNNanjing University of Chinese Medicine · CN

Funding

China Postdoctoral Science Foundation 2018M642373'Double First-Class' University project CPU2018GF05'Double First-Class' University project CPU2018GF11Drug Innovation Major Project 2017ZX09101003-005-023Drug Innovation Major Project 2017ZX09301014Drug Innovation Major Project 2018ZX09711001-003-007Nanjing Medical Science and Technology Development Project YKK17074National Natural Science Foundation of China 81503096National Natural Science Foundation of China 81673461National Natural Science Foundation of China 81830105National Natural Science Foundation of China 81873046National Natural Science Foundation of China 81903647Natural Science Foundation of Jiangsu province BE2018711Natural Science Foundation of Jiangsu province BK20190560Program for Changjiang Scholars and Innovative Research Team in University IRT1193Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University SKLNMZZCX201823Research and Innovation Project for College Graduates of Jiangsu Province KYCX18_0803
6 · The paper itself

Abstract

backgroundAlthough targeting histone deacetylases (HDACs) may be an effective strategy for core binding factor-acute myeloid leukemia (CBF-AML) harboring t(8;21) or inv(16), HDAC inhibitors are reported to be limited by drug-resistant characteristic. Our purpose is to evaluate the anti-leukemia effects of Baicalein on CBF-AML and clarify its underlying mechanism.

methodsEnzyme activity assay was used to measure the activity inhibition of HDACs. Rhodamine123 and RT-qPCR were employed to evaluate the distribution of drugs and the change of ATP-binding cassette (ABC) transporter genes. CCK8, Annexin V/PI, and FACS staining certified the effects of Baicalein on cell growth, apoptosis, and differentiation. Duolink and IP assay assessed the interaction between HDAC-1 and ubiquitin, HSP90 and AML1-ETO, and Ac-p53 and CBFβ-MYH11. AML cell lines and primary AML cells-bearing NOD/SCID mice models were used to evaluate the anti-leukemic efficiency and potential mechanism of Baicalein in vivo.

resultsBaicalein showed HDAC-1/8 inhibition to trigger growth suppression and differentiation induction of AML cell lines and primary AML cells. Although the inhibitory action on HDAC-1 was mild, Baicalein could induce the degradation of HDAC-1 via ubiquitin proteasome pathway, thereby upregulating the acetylation of Histone H3 without promoting ABC transporter genes expression. Meanwhile, Baicalein increased the acetylation of HSP90 and lessened its connection to AML1/ETO, consequently leading to degradation of AML1-ETO in t(8;21)q(22;22) AML cells. In inv(16) AML cells, Baicalein possessed the capacity of apoptosis induction accompanied with p53-mediated apoptosis genes expression. Moreover, CBFβ-MYH11-bound p53 acetylation was restored via HDAC-8 inhibition induced by Baicalein contributing the diminishing of survival of CD34

conclusionsThese findings improved the understanding of the epigenetic regulation of Baicalein, and warrant therapeutic potential of Baicalein for CBF-AML.

Indexed as

ABC transporter genesCBF-AMLdifferentiationHDAC-1/8 inhibitorsnatural product

Identifiers

PMID32898337
PMCPMC7449246
OpenAlexW3081795290

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Registered trials

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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.