Evidence map›Paper›PMID 30685490›Full record

ArticleMitochondrion2019

Withaferin A-mediated apoptosis in breast cancer cells is associated with alterations in mitochondrial dynamics.

Anuradha Sehrawat, Suman K Samanta, Eun-Ryeong Hahm, Claudette St Croix, Simon Watkins, Shivendra V Singh

Open access · greenAbstract read
In one paragraph

Article in Mitochondrion, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
9.9field-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

25 citing papers in PubMed, 52 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

6 authors at 1 institution in 2 countries.

Anuradha SehrawatDepartment of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Suman K SamantaDepartment of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Life Sciences Division, Institute of Advanced Study in Science and Technology, Guwahati, India.
Eun-Ryeong HahmDepartment of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Claudette St CroixDepartment of Cell Biology, University of Pittsburgh, Pittsburgh, PA, USA.
Simon WatkinsDepartment of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Shivendra V SinghDepartment of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; UPMC Hillman Cancer Center, Pittsburgh, PA, USA. Electronic address: singhs@upmc.edu.
University of Pittsburgh · US

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Jessie Nedrow · 1988 to 2026
$158.0M
Breast Cancer Prevention by Ayurvedic Medicine ConstituentsR01CA142604 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SINGH, SHIVENDRA · 2010 to 2019
$3.2M
Breast Cancer Prevention by Dietary PhytochemicalsR01CA129347 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SINGH, SHIVENDRA · 2007 to 2016
$2.8M
NCI NIH HHS P30 CA047904NCI NIH HHS R01 CA129347NCI NIH HHS R01 CA142604
6 · The paper itself

Abstract

Withaferin A (WA), a steroidal lactone derived from a medicinal plant (Withania somnifera), inhibits cancer development in transgenic and chemically-induced rodent models of breast cancer but the underlying mechanism is not fully grasped. We have shown previously that WA treatment causes apoptotic cell death in human breast cancer cells that is preceded by inhibition of complex III of the mitochondrial electron transport chain. This study extends these observations to now demonstrate alterations in mitochondrial dynamics in WA-induced apoptosis. Assembly of complex III was decreased in MCF-7 and SUM159 cells but not in MDA-MB-231 as determined by native blue gel electrophoresis. Because WA is a Michael acceptor (electrophile), we explored the possibility of whether it covalently modifies cysteine residue(s) in ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1 (UQCRFS1). Covalent modification of cysteine in UQCRFS1 was not observed after WA treatment. Instead, WA treatment inhibited chemically-induced mitochondrial fusion and decreased the mitochondrial volume, and this effect was accompanied by a decrease in the expression of proteins involved in fusion process, including mitofusin1, mitofusin2, and full-length optic atrophy protein 1 (OPA1). A loss of volume in fragmented mitochondria also occurred in WA-exposed cells when compared to vehicle-treated control. WA treatment also caused a decrease in protein level of mitochondrial fission-regulating protein dynamin-related protein 1 (DRP1). Functional studies revealed that DRP1 deficiency and OPA1 knockdown attenuated apoptotic potential of WA. Taken together, these results indicate that WA not only alters Complex III assembly but also inhibits mitochondrial dynamics in breast cancer cells.

Indexed as

ApoptosisBreast NeoplasmsFemaleGene Expression Regulation, NeoplasticHumansMCF-7 CellsMitochondriaMitochondrial DynamicsMitochondrial ProteinsNeoplasm ProteinsWithanolidesMitochondrial ProteinsNeoplasm Proteinswithaferin AWithanolidesApoptosisBreast cancerChemopreventionMitochondrial dynamicsWithaferin A

Identifiers

PMID30685490
PMCPMC6599725
OpenAlexW2912465277

What OpenQuestion holds

Textmetadata
LicenceTDM
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.