Evidence map›Paper›PMID 37666118›Full record

ArticleRedox biology2023

Oxidative stress mediates the inhibitory effects of Manzamine A on uterine leiomyoma cell proliferation and extracellular matrix deposition via SOAT inhibition.

Li-Chun Lin, Hsin-Yi Chang, Tzu-Ting Kuo, Hsin-Yuan Chen, Wen-Shan Liu, Yii-Jwu Lo, Shih-Min Hsia, Tsui-Chin Huang

Open access · goldAbstract read
In one paragraph

Article in Redox biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
5.5field-weighted citation impact, top 4% 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

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 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

8 authors at 3 institutions in 1 country.

Li-Chun LinPhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, 11031, Taiwan; School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, 11031, Taiwan.
Hsin-Yi ChangGraduate Institute of Medical Sciences, National Defense Medical Center, Taipei, 11031, Taiwan; Department of Research and Development, National Defense Medical Center, Taipei, Taiwan.
Tzu-Ting KuoPhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, 11031, Taiwan.
Hsin-Yuan ChenSchool of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, 11031, Taiwan.
Wen-Shan LiuGraduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, 11031, Taiwan.
Yii-Jwu LoGraduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei, 11031, Taiwan.
Shih-Min HsiaSchool of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, 11031, Taiwan; Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei, 11031, Taiwan; School of Food Safety, College of Nutrition, Taipei Medical University, Taipei, 11031, Taiwan.
Tsui-Chin HuangPhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, 11031, Taiwan; Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, 11031, Taiwan; Master Program in Clinical Pharmacogenomics and Pharmacoproteomics, College of Pharmacy, Taipei Medical University, Taipei, 11031, Taiwan; TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, 11031, Taiwan; Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei, 11031, Taiwan. Electronic address: tsuichin@tmu.edu.tw.
Taipei Medical University · TWNational Defense Medical Center · TWTaipei Medical University Hospital · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Uterine fibroids, the most common benign tumors of the myometrium in women, are characterized by abnormal extracellular matrix deposition and uterine smooth muscle cell neoplasia, with high recurrence rates. Here, we investigated the potential of the marine natural product manzamine A (Manz A), which has potent anti-cancer effects, as a treatment for uterine fibroids. Manz A inhibited leiomyoma cell proliferation in vitro and in vivo by arresting cell cycle progression and inducing caspase-mediated apoptosis. We performed target prediction analysis and identified sterol o-acyltransferases (SOATs) as potential targets of Manz A. Cholesterol esterification and lipid droplet formation were reduced by Manz A, in line with reduced SOAT expression. As a downstream target of SOAT, Manz A also prevented extracellular matrix deposition by inhibiting the β-catenin/fibronectin/metalloproteinases axis and enhanced autophagy turnover. Excessive free fatty acid accumulation by SOAT inhibition led to reactive oxygen species to impair mitochondrial oxidative phosphorylation and trigger endoplasmic reticulum stress via PERK/eIF2α/CHOP signaling. The inhibitory effect of ManzA on cell proliferation was partially restored by PERK knockdown and eliminated by tauroursodeoxycholic acid, suggesting oxidative stress plays a critical role in the mechanism of action of Manz A. These findings suggest that targeting SOATs by Manz A may be a promising therapeutic approach for uterine fibroids.

Indexed as

LeiomyomaOxidative StressCarbazolesCell ProliferationFemaleHumansCarbazolesmanzamine ACholesterol esterificationER stressManzamine AOxidative stressSOATUterine fibroid

Identifiers

PMID37666118
PMCPMC10491796
OpenAlexW4386170625

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.