Evidence map›Paper›PMID 39238058›Full record

ArticleCell & bioscience2024

Targeting stress induction of GRP78 by cardiac glycoside oleandrin dually suppresses cancer and COVID-19.

Dat P Ha, Woo-Jin Shin, Ze Liu, Michael E Doche, Roy Lau, Nektaria Maria Leli, Crystal S Conn, Mariangela Russo, Annalisa Lorenzato, Constantinos Koumenis and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell & bioscience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
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

6 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Molecular mechanisms of SARS-CoV-2 entry: implications for biomedical strategies.Microbiology and molecular biology reviews : MMBR · 2025
    Review
  5. Stress-induced translocation of the endoplasmic reticulum chaperone GRP78/BiP and its impact on human disease and therapy.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  6. Review
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.

Dat P Ha *Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
Woo-Jin Shin *Florida Research and Innovation Center, Cleveland Clinic, Port St. Lucie, FL, 34987, USA.
Ze Liu *Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
Michael E DocheEllison Institute of Technology, Los Angeles, CA, 90064, USA.
Roy LauEllison Institute of Technology, Los Angeles, CA, 90064, USA.
Nektaria Maria LeliDepartment of Radiation Oncology, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Crystal S ConnDepartment of Radiation Oncology, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Mariangela RussoDipartimento di Oncologia, Molecular Biotechnology Center, Università di Torino, Turin, Italy.
Annalisa LorenzatoDipartimento di Oncologia, Molecular Biotechnology Center, Università di Torino, Turin, Italy.
Constantinos KoumenisDepartment of Radiation Oncology, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Min YuNorris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
Shannon M MumenthalerNorris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
Amy S LeeDepartment of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA. amylee@usc.edu.ORCID http://orcid.org/0000-0002-0378-5443

Funding

STRESS INDUCTION OF THE GLUCOSE REGULATED PROTEINSR01CA027607 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI LEE, AMY S · 1985 to 2021
$11.1M
Targeting Cancer through Suppressing Stress Induction of GRP78/BiPR01CA238029 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI LEE, AMY S · 2020 to 2022
$1.1M
Italian Association for Cancer Research MFAG 2021-ID 26439NIH HHS R01 CA027607NIH HHS R01 CA238029
6 · The paper itself

Abstract

backgroundDespite recent therapeutic advances, combating cancer resistance remains a formidable challenge. The 78-kilodalton glucose-regulated protein (GRP78), a key stress-inducible endoplasmic reticulum (ER) chaperone, plays a crucial role in both cancer cell survival and stress adaptation. GRP78 is also upregulated during SARS-CoV-2 infection and acts as a critical host factor. Recently, we discovered cardiac glycosides (CGs) as novel suppressors of GRP78 stress induction through a high-throughput screen of clinically relevant compound libraries. This study aims to test the possibility that agents capable of blocking stress induction of GRP78 could dually suppress cancer and COVID-19.

resultsHere we report that oleandrin (OLN), is the most potent among the CGs in inhibiting acute stress induction of total GRP78, which also results in reduced cell surface and nuclear forms of GRP78 in stressed cells. The inhibition of stress induction of GRP78 is at the post-transcriptional level, independent of protein degradation and autophagy and may involve translational control as OLN blocks stress-induced loading of ribosomes onto GRP78 mRNAs. Moreover, the human Na

conclusionOur findings validate GRP78 as a target of OLN anti-cancer and anti-viral activities. These proof-of-principle studies support further investigation of OLN as a readily accessible compound to dually combat cancer and COVID-19.

Indexed as

Anti-cancer therapyAnti-viral therapyBreast cancerCardiac glycosidesColon cancerER stressGRP78OleandrinSARS-CoV-2

Identifiers

PMID39238058
PMCPMC11378597

What OpenQuestion holds

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Registered trials

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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.