Evidence map›Paper›PMID 21555592›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2011

Apogossypol derivative BI-97C1 (Sabutoclax) targeting Mcl-1 sensitizes prostate cancer cells to mda-7/IL-24-mediated toxicity.

Rupesh Dash, Belal Azab, Bridget A Quinn, Xuening Shen, Xiang-Yang Wang, Swadesh K Das, Mohamed Rahmani, Jun Wei, Michael Hedvat, Paul Dent and 9 more

Erratum issuedAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 73 papers.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed
7.7field-weighted citation impact, top 2% 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

73 citing papers in PubMed, 124 citations in OpenAlex.

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  18. Alveolar Macrophage Apoptosis-associated Bacterial Killing Helps Prevent Murine Pneumonia.American journal of respiratory and critical care medicine · 2019
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13 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 3 institutions in 1 country.

Rupesh DashDepartment of Human and Molecular Genetics, Virginia Commonwealth University Institute of Molecular Medicine, and Virginia Commonwealth University Massey Cancer Center, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
Belal Azab
Bridget A Quinn
Xuening Shen
Xiang-Yang Wang
Swadesh K Das
Mohamed Rahmani
Jun Wei
Michael Hedvat
Paul Dent
Igor P Dmitriev
David T Curiel
Steven Grant
Bainan Wu
John L Stebbins
Maurizio Pellecchia
John C Reed
Devanand Sarkar
Paul B Fisher
Sanford Burnham Prebys Medical Discovery Institute · USVirginia Commonwealth University · USWashington University in St. Louis · US

Funding

Translational Applications of mda-7/IL-24 in CancerP01CA104177 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI FISHER, PAUL B · 2005 to 2009
$6.5M
SIGNALING PATHWAYS REGULATING EPITHELIAL CELL SURVIVALR01DK052825 · NIDDK · VIRGINIA COMMONWEALTH UNIVERSITY · PI DENT, PAUL · 1999 to 2013
$3.3M
MDA-7: Novel Cancer Therapeutic GeneR01CA097318 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI FISHER, PAUL B · 2002 to 2012
$2.8M
Interplay between tumor and microenvironment in bone metastasisR01CA259599 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI FISHER, PAUL B, WANG, XIANG-YANG SHAWN · 2021 to 2025
$2.3M
Targeting apoptosis via chemical design of Bcl-2 antagonistsR01CA149668 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI PELLECCHIA, MAURIZIO · 2010 to 2014
$1.9M
OSU-03012 therapy for glioblastomaR01CA141703 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI DENT, PAUL · 2010 to 2014
$1.5M
Lapatinib and Obatoclax combination therapyR01CA150214 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI DENT, PAUL · 2010 to 2014
$1.5M
Pancreatic Cancer Management by Novel Gene Therapy & Dietary AgentsR01CA127641 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI FISHER, PAUL B · 2009 to 2012
$1.2M
NCI NIH HHS P01 CA104177NCI NIH HHS R01 CA097318NCI NIH HHS R01 CA127641NCI NIH HHS R01 CA141703NCI NIH HHS R01 CA149668NCI NIH HHS R01 CA150214NCI NIH HHS R01 CA259599NIDDK NIH HHS R01 DK052825
6 · The paper itself

Abstract

Limited options are available for treating patients with advanced prostate cancer (PC). Melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24), an IL-10 family cytokine, exhibits pleiotropic anticancer activities without adversely affecting normal cells. We previously demonstrated that suppression of the prosurvival Bcl-2 family member, myeloid cell leukemia-1 (Mcl-1), is required for mda-7/IL-24-mediated apoptosis of prostate carcinomas. Here we demonstrate that pharmacological inhibition of Mcl-1 expression with the unique Apogossypol derivative BI-97C1, also called Sabutoclax, is sufficient to sensitize prostate tumors to mda-7/IL-24-induced apoptosis, whereas ABT-737, which lacks efficacy in inhibiting Mcl-1, does not sensitize mda-7/IL-24-mediated cytotoxicity. A combination regimen of tropism-modified adenovirus delivered mda-7/IL-24 (Ad.5/3-mda-7) and BI-97C1 enhances cytotoxicity in human PC cells, including those resistant to mda-7/IL-24 or BI-97C1 alone. The combination regimen causes autophagy that facilitates NOXA- and Bim-induced and Bak/Bax-mediated mitochondrial apoptosis. Treatment with Ad.5/3-mda-7 and BI-97C1 significantly inhibits the growth of human PC xenografts in nude mice and spontaneously induced PC in Hi-myc transgenic mice. Tumor growth inhibition correlated with increased TUNEL staining and decreased Ki-67 expression in both PC xenografts and prostates of Hi-myc mice. These findings demonstrate that pharmacological inhibition of Mcl-1 with the Apogossypol derivative, BI-97C1, sensitizes human PCs to mda-7/IL-24-mediated cytotoxicity, thus potentially augmenting the therapeutic benefit of this combinatorial approach toward PC.

Indexed as

AnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisCell Line, TumorGenetic TherapyGossypolHumansInterleukin-24InterleukinsMaleMiceMice, NudeMyeloid Cell Leukemia Sequence 1 ProteinProstatic NeoplasmsProto-Oncogene Proteins c-bcl-2Transfection1,1',6,6',7,7'-hexahydroxy-3,3'-dimethyl-N5-(2-phenylpropyl)-N5'-(2-phenylpropyl)-2,2'-binaphthyl-5,5'-dicarboxamideapogossypolGossypolInterleukin-24InterleukinsMcl1 protein, mouseMyeloid Cell Leukemia Sequence 1 ProteinProto-Oncogene Proteins c-bcl-2

Identifiers

PMID21555592
PMCPMC3102401
OpenAlexW2006366803

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.