Evidence map›Paper›PMID 30704503›Full record

ArticleJournal of experimental & clinical cancer research : CR2019

CYT997(Lexibulin) induces apoptosis and autophagy through the activation of mutually reinforced ER stress and ROS in osteosarcoma.

Zongyi Wang, Fei Yin, Jing Xu, Tao Zhang, Gangyang Wang, Ming Mao, Zhuoying Wang, Wei Sun, Jing Han, Mengkai Yang and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
6.4field-weighted citation impact, top 3% 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

58 citing papers in PubMed, 110 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

13 authors at 2 institutions in 1 country.

Zongyi WangDepartment of Orthopaedics, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Poster address: 100 Haining Road Shanghai, Shanghai, 20160, China.
Fei YinDepartment of Orthopaedics, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Poster address: 100 Haining Road Shanghai, Shanghai, 20160, China.
Jing XuDepartment of Orthopaedics, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Poster address: 100 Haining Road Shanghai, Shanghai, 20160, China.
Tao ZhangDepartment of Orthopaedics, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Poster address: 100 Haining Road Shanghai, Shanghai, 20160, China.
Gangyang WangDepartment of Orthopaedics, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Poster address: 100 Haining Road Shanghai, Shanghai, 20160, China.
Ming MaoDepartment of Orthopaedics, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Poster address: 100 Haining Road Shanghai, Shanghai, 20160, China.
Zhuoying WangDepartment of Orthopaedics, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Poster address: 100 Haining Road Shanghai, Shanghai, 20160, China.
Wei SunDepartment of Orthopaedics, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Poster address: 100 Haining Road Shanghai, Shanghai, 20160, China.
Jing HanDepartment of Orthopaedics, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Poster address: 100 Haining Road Shanghai, Shanghai, 20160, China.
Mengkai YangDepartment of Orthopaedics, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Poster address: 100 Haining Road Shanghai, Shanghai, 20160, China.
Yafei JiangDepartment of Orthopaedics, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Poster address: 100 Haining Road Shanghai, Shanghai, 20160, China.
Yingqi HuaDepartment of Orthopaedics, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Poster address: 100 Haining Road Shanghai, Shanghai, 20160, China. yhua@shsmu.edu.cn.
Zhengdong CaiDepartment of Orthopaedics, Shanghai Bone Tumor Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Poster address: 100 Haining Road Shanghai, Shanghai, 20160, China. czd856@vip.163.com.
Shanghai First People's Hospital · CNShanghai Jiao Tong University · CN

Funding

National Natural Science Foundation of China 81702973National Natural Science Foundation of China 81772859Young Scientists Fund 81501584Young Scientists Fund 81502604
6 · The paper itself

Abstract

backgroundOsteosarcoma (OS) is a common malignant cancer in children and adolescents and has a cure rate that has not improved in the last two decades. CYT997 (lexibulin) is a novel potent microtubule-targeting agent with various anticancer activities, such as proliferation inhibition, vascular disruption, and cell cycle arrest and apoptosis induction, in multiple cancers. However, the direct cytotoxic mechanisms of CYT997 have not yet been fully characterized.

methodsWe evaluated apoptosis and autophagy in human osteosarcomas after treatment with CYT997 and investigated the underlying mechanisms. To explore relationships, we used the reactive oxygen species (ROS) scavenger N-acetyl cysteine (NAC), PERK inhibitor GSK2606414, ERO1 inhibitor EN460 and mitochondrial targeted protection peptide elamipretide. BALB/c-nu mice were inoculated with 143B tumor cells to investigate the in vivo effect of CYT997.

resultsWe explored the efficacy and mechanism of CYT997 in osteosarcoma (OS) in vitro and in vivo and demonstrated that CYT997 potently suppresses cell viability and induces apoptosis and autophagy. CYT997 triggered production of ROS and exerted lethal effects via endoplasmic reticulum (ER) stress in OS cells. NAC attenuated these effects. The PERK inhibitor GSK2606414, which can block the ER stress pathway, reduced ROS production and enhanced cell viability. Moreover, activation of ERO1 in the ER stress pathway was responsible for inducing ROS production. ROS produced by the mitochondrial pathway also aggravate ER stress. Protection of mitochondria can reduce apoptosis and autophagy. Finally, CYT997 prominently reduced tumor growth in vivo.

conclusionsThis study suggests that CYT997 induces apoptosis and autophagy in OS cells by triggering mutually enhanced ER stress and ROS and may thus be a promising agent against OS.

Indexed as

AutophagyAnimalsApoptosisBone NeoplasmsCell CycleCell ProliferationEndoplasmic Reticulum StressFemaleHumansMiceMice, Inbred BALB CMice, NudeMitochondriaOsteosarcomaPyridinesPyrimidinesCYT997PyridinesPyrimidinesReactive Oxygen SpeciesCYT997ERO1AER stressOsteosarcomaROS

Identifiers

PMID30704503
PMCPMC6357486
OpenAlexW2921327900

What OpenQuestion holds

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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.