Evidence map›Paper›PMID 28454099›Full record

ArticleOncotarget2017

Homoharringtonine targets Smad3 and TGF-β pathway to inhibit the proliferation of acute myeloid leukemia cells.

Jian Chen, Qitian Mu, Xia Li, Xiufeng Yin, Mengxia Yu, Jing Jin, Chenying Li, Yile Zhou, Jiani Zhou, Shanshan Suo and 2 more

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

18 citing papers in PubMed, 31 citations in OpenAlex.

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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 at 3 institutions in 1 country.

Jian ChenDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Qitian MuDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Xia LiDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Xiufeng YinDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Mengxia YuDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Jing JinDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Chenying LiDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Yile ZhouDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Jiani ZhouDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Shanshan SuoDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Demin LuDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Jie JinDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
First Affiliated Hospital Zhejiang University · CNZhejiang University · CNNingbo First Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Homoharringtonine (HHT) has long and widely been used in China for the treatment of acute myeloid leukemia (AML), the clinical therapeutic effect is significant but the working mechanism is poorly understood. The purpose of this study is to screen the possible target for HHT with virtual screening and verify the findings by cell experiments. Software including Autodock, Python, and MGL tools were used, with HHT being the ligand and proteins from PI3K-Akt pathway, Jak-stat pathway, TGF-β pathway and NK-κB pathway as the receptors. Human AML cell lines including U937, KG-1, THP-1 were cultured and used as the experiment cell lines. MTT assay was used for proliferation detection, flowcytometry was used to detect apoptosis and cell cycle arrest upon HHT functioning, western blotting was used to detect the protein level changes, viral shRNA transfection was used to suppress the expression level of the target protein candidate, and viral mRNA transfection was used for over-expression. Virtual screening revealed that smad3 from TGF-β pathway might be the candidate for HHT binding. In AML cell line U937 and KG-1, HHT can induce the Ser423/425 phosphorylation of smad3, and this phosphorylation can subsequently activate the TGF-β pathway, causing cell cycle arrest at G1 phase in U937 cells and apoptosis in KG-1 cells, knockdown of smad3 can impair the sensitivity of U937 cell to HHT, and over-expression of smad3 can re-establish the sensitivity in both cell lines. We conclude that smad3 is the probable target protein of HHT and plays an important role in the functioning mechanism of HHT.

Indexed as

Antineoplastic Agents, PhytogenicApoptosisCell Line, TumorCell ProliferationG1 Phase Cell Cycle CheckpointsHarringtoninesHomoharringtonineHumansLeukemia, Myeloid, AcutePhosphorylationRNA InterferenceRNA, Small InterferingSmad3 ProteinTHP-1 CellsTransforming Growth Factor betaU937 CellsAntineoplastic Agents, PhytogenicHarringtoninesHomoharringtonineRNA, Small InterferingSmad3 ProteinSMAD3 protein, humanTransforming Growth Factor betaacute myeloid leukemiahomoharringtoninesmad3TGF-β

Identifiers

PMID28454099
PMCPMC5522237
OpenAlexW2605308508

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.