Evidence map›Paper›PMID 18794155›Full record

ArticleCancer research2008

Withaferin A causes FOXO3a- and Bim-dependent apoptosis and inhibits growth of human breast cancer cells in vivo.

Silvia D Stan, Eun-Ryeong Hahm, Renaud Warin, Shivendra V Singh

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

Article in Cancer research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers.

0numbers the graph read from it
0cells of the map it votes in
145citing papers in PubMed
35.6field-weighted citation impact, top 1% 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

145 citing papers in PubMed, 259 citations in OpenAlex.

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  16. Withaferin A and Celastrol Overwhelm Proteostasis.International journal of molecular sciences · 2023
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85 more citing papers are in PubMed but not listed here.

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

4 authors at 1 institution in 1 country.

Silvia D StanDepartment of Pharmacology and Chemical Biology, and University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Eun-Ryeong Hahm
Renaud Warin
Shivendra V Singh
UPMC Hillman Cancer Center · US

Funding

Breast Cancer Prevention by Dietary PhytochemicalsR01CA129347 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SINGH, SHIVENDRA · 2007 to 2016
$2.8M
NCI NIH HHS CA129347NCI NIH HHS R01 CA129347
6 · The paper itself

Abstract

Withaferin A (WA) is derived from the medicinal plant Withania somnifera, which has been safely used for centuries in Indian Ayurvedic medicine for treatment of different ailments. We now show, for the first time, that WA exhibits significant activity against human breast cancer cells in culture and in vivo. The WA treatment decreased viability of MCF-7 (estrogen-responsive) and MDA-MB-231 (estrogen-independent) human breast cancer cells in a concentration-dependent manner. The WA-mediated suppression of breast cancer cell viability correlated with apoptosis induction characterized by DNA condensation, cytoplasmic histone-associated DNA fragmentation, and cleavage of poly-(ADP-ribose)-polymerase. On the other hand, a spontaneously immortalized normal mammary epithelial cell line (MCF-10A) was relatively more resistant to WA-induced apoptosis compared with breast cancer cells. The WA-mediated apoptosis was accompanied by induction of Bim-s and Bim-L in MCF-7 cells and induction of Bim-s and Bim-EL isoforms in MDA-MB-231 cells. The cytoplasmic histone-associated DNA fragmentation resulting from WA exposure was significantly attenuated by knockdown of protein levels of Bim and its transcriptional regulator FOXO3a in both cell lines. Moreover, FOXO3a knockdown conferred marked protection against WA-mediated induction of Bim-s expression. The growth of MDA-MB-231 cells implanted in female nude mice was significantly retarded by 5 weekly i.p. injections of 4 mg WA/kg body weight. The tumors from WA-treated mice exhibited reduced cell proliferation and increased apoptosis compared with tumors from control mice. These results point toward an important role of FOXO3a and Bim in regulation of WA-mediated apoptosis in human breast cancer cells.

Indexed as

AnimalsAntineoplastic Agents, PhytogenicApoptosisApoptosis Regulatory ProteinsBcl-2-Like Protein 11Breast NeoplasmsCell Growth ProcessesCell Line, TumorErgosterolFemaleForkhead Box Protein O3Forkhead Transcription FactorsHumansMembrane ProteinsMiceMice, NudeAntineoplastic Agents, PhytogenicApoptosis Regulatory ProteinsBCL2L11 protein, humanBcl2l11 protein, mouseBcl-2-Like Protein 11ErgosterolForkhead Box Protein O3Forkhead Transcription FactorsFOXO3 protein, humanMembrane ProteinsProto-Oncogene ProteinsRNA, Small Interferingwithaferin AWithanolides

Identifiers

PMID18794155
PMCPMC2562581
OpenAlexW2077173514

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.