Evidence map›Paper›PMID 29773887›Full record

ArticleActa pharmacologica Sinica2019

Varacin-1, a novel analog of varacin C, induces p53-independent apoptosis in cancer cells through ROS-mediated reduction of XIAP.

Jing Zhou, Wen-Li Li, Zi-Xuan Wang, Nai-Yuan Chen, Yue Tang, Xiao-Xiao Hu, Jing-Huan Deng, Yixin Lu, Guo-Dong Lu

Open access · bronzeAbstract read
In one paragraph

Article in Acta pharmacologica Sinica, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.2field-weighted citation impact, top 47% 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

2 citing papers in PubMed, 5 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

9 authors at 3 institutions in 2 countries.

Jing ZhouDepartment of Physiology, School of Preclinical Medicine, Guangxi Medical University, Nanning, 530021, China.
Wen-Li LiGuangdong Provincial Center for Disease Control and Prevention, Guangzhou, 511430, China.
Zi-Xuan WangDepartment of Toxicology, School of Public Health, Guangxi Medical University, Nanning, 530021, China.
Nai-Yuan ChenGuangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, 530021, China.
Yue TangDepartment of Toxicology, School of Public Health, Guangxi Medical University, Nanning, 530021, China.
Xiao-Xiao HuDepartment of Toxicology, School of Public Health, Guangxi Medical University, Nanning, 530021, China.
Jing-Huan DengGuangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, 530021, China.
Yixin LuDepartment of Chemistry, National University of Singapore, Singapore, 117543, Singapore.
Guo-Dong LuDepartment of Toxicology, School of Public Health, Guangxi Medical University, Nanning, 530021, China. golden_lu@hotmail.com.
Guangxi Medical University · CNGuangdong Provincial Center for Disease Control and Prevention · CNNational University of Singapore · SG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Varacin C is a promising anticancer agent and possesses acid-promoted and photo-induced DNA-damaging activities. In this study, we synthesized an analog varacin-1 (VCA-1) and examined its anticancer potentials. The results demonstrated that VCA-1 caused dose-dependent apoptotic cell death in cancer cells. Note that this action is independent of p53 status, because VCA-1 induced similar levels of apoptosis in two different panels of cell lines (HCT116 p53- wild-type vs. HCT116 p53-knockout colon cancer cells, and p53-expressing U2OS vs. p53-deficient saos2 osteosarcoma cancer cells). VCA-1-induced apoptosis was found to be mainly via the extrinsic apoptosis pathway involving caspase-8 activation and XIAP reduction. Forced over-expression of XIAP markedly prevented apoptosis, indicating its essential role in VCA-1 induced apoptosis. On the other hand, VCA-1 treatment enhanced intracellular ROS (reactive oxygen species) generation also in a p53-independent manner, and consequently promoted caspase activation. Pretreatment of N-acetyl cysteine (an antioxidant), rather than z-VAD (specific caspase inhibitor), markedly prevented XIAP reduction, suggesting that XIAP reduction may be resulted from oxidative stress. In conclusion, data from this study reveal the essential roles of ROS generation and XIAP reduction in VCA-1-induced apoptosis in cancer cells. VCA-1 may be a novel cancer therapeutic agent, especially in p53-mutant human cancers.

Indexed as

Antineoplastic AgentsApoptosisCell Line, TumorCyclic S-OxidesEthylaminesHumansReactive Oxygen SpeciesSulfidesX-Linked Inhibitor of Apoptosis ProteinAntineoplastic AgentsCyclic S-OxidesEthylaminesReactive Oxygen SpeciesSulfidesXIAP protein, humanX-Linked Inhibitor of Apoptosis Proteinapoptosisp53ROSvaracin-1XIAP

Identifiers

PMID29773887
PMCPMC6329757
OpenAlexW2803995829

What OpenQuestion holds

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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.