Evidence map›Paper›PMID 31285958›Full record

ArticleAmerican journal of cancer research2019

Induction of autophagy-dependent apoptosis in cancer cells through activation of ER stress: an uncovered anti-cancer mechanism by anti-alcoholism drug disulfiram.

Xiao Zhang, Pan Hu, Shi-Ying Ding, Ting Sun, Ling Liu, Shiwei Han, Albert B DeLeo, Ananthan Sadagopan, Wei Guo, Xinhui Wang

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

Article in American journal of cancer research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
6.2field-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

50 citing papers in PubMed, 63 citations in OpenAlex.

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  18. Activation of autophagy byBioactive materials · 2023
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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

10 authors at 1 institution in 1 country.

Xiao ZhangDivision of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Harvard Medical School Boston, MA, USA.
Pan HuDivision of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Harvard Medical School Boston, MA, USA.
Shi-Ying DingDepartment of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School Boston, MA, USA.
Ting SunDivision of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Harvard Medical School Boston, MA, USA.
Ling LiuDivision of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Harvard Medical School Boston, MA, USA.
Shiwei HanDivision of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Harvard Medical School Boston, MA, USA.
Albert B DeLeoDivision of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Harvard Medical School Boston, MA, USA.
Ananthan SadagopanDivision of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Harvard Medical School Boston, MA, USA.
Wei GuoDivision of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Harvard Medical School Boston, MA, USA.
Xinhui WangDivision of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Harvard Medical School Boston, MA, USA.
Harvard University · US

Funding

Prevention of post-therapy breast cancer metastasisR01CA226981 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI WANG, XINHUI · 2019 to 2023
$1.8M
Improving Radiation Therapy For Pancreatic CancerR21CA181851 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI WANG, XINHUI · 2015 to 2016
$407k
NCI NIH HHS R01 CA226981NCI NIH HHS R21 CA181851
6 · The paper itself

Abstract

Due to its potent anticancer activity, there is interest in repurposing of the FDA-approved anti-alcoholism drug, disulfiram (DSF). DSF forms potent complexes with copper (DSF/Cu) that induce apoptosis of many types of cancer cells. Here, we investigated the role of DSF/Cu in autophagy, a mechanism of cell death or survival, and its interplay with DSF/Cu induced apoptosis of human pancreatic and breast cancer cells.

methodsLevels of autophagy and apoptosis were assessed by Western blot, flow cytometry and immunofluorescence analysis. Cell viability was measured by MTT assays. Activation of inositol-requiring enzyme 1α (IRE1α)-mRNA X-box binding protein 1 (XBP1) pathway and spliced XBP1 (XBP1s) expression were analyzed by Western blot, Phos-tag gel assay, RT-PCR, qRT-PCR and flow cytometry.

resultsThe apoptosis induced by DSF/Cu in pancreatic and breast cancer cells is autophagy dependent. This is accomplished by activating IRE1α, the sensor of unfolded protein response (UPR) via promotion of phosphorylation of IRE1α and its downstream XBP1 splicing into active XBP1s.

conclusionsDSF/Cu induces ER-stress through activation of IRE1α-XBP1 pathway which is responsible, at least in part, for induction of autophagy-dependent apoptosis of cancer cells. Insight into the ER-stress inducing ability by DSF/Cu may open a new research area for rational design of innovative therapeutic strategies for pancreatic and breast cancers.

Indexed as

apoptosiscancercytotoxic autophagyDisulfiramER stressIRE1α pathwayXBP1s

Identifiers

PMID31285958
PMCPMC6610050
OpenAlexW2981637832

What OpenQuestion holds

Textmetadata
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.