Evidence map›Paper›PMID 31138329›Full record

ArticleJournal of experimental & clinical cancer research : CR2019

ROS-mediated activation and mitochondrial translocation of CaMKII contributes to Drp1-dependent mitochondrial fission and apoptosis in triple-negative breast cancer cells by isorhamnetin and chloroquine.

Jinjiao Hu, Yanhao Zhang, Xiuxing Jiang, Hongwei Zhang, Ziyi Gao, Yunong Li, Ruoqiu Fu, Lirong Li, Jie Li, Hongjuan Cui and 1 more

Open access · goldAbstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed, 2 pooled it
4.6field-weighted citation impact, top 4% 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

87 citing papers in PubMed, 2 syntheses or guidelines pooled it, 138 citations in OpenAlex.

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27 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

11 authors at 4 institutions in 2 countries.

Jinjiao HuCollege of Pharmacy, Army Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing, 400038, China.
Yanhao ZhangCollege of Pharmacy, Army Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing, 400038, China.
Xiuxing JiangCollege of Pharmacy, Army Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing, 400038, China.
Hongwei ZhangCollege of Pharmacy, Army Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing, 400038, China.
Ziyi GaoGreater Philadelphia Pharmacy, Philadelphia, USA.
Yunong LiCollege of Pharmacy, Army Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing, 400038, China.
Ruoqiu FuCollege of Pharmacy, Army Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing, 400038, China.
Lirong LiCollege of Pharmacy, Army Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing, 400038, China.
Jie LiCollege of Pharmacy, Army Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing, 400038, China.
Hongjuan CuiState Key Laboratory of Silkworm Genome Biology, Southwest University, 2#Tiansheng Road, Beibei District, Chongqing, 400716, China. hongjuan.cui@gmail.com.
Ning GaoCollege of Pharmacy, Army Medical University, 30 Gaotanyan Street, Shapingba District, Chongqing, 400038, China. gaoning59@163.com.
Army Medical University · CNPhiladelphia University · USSouthwest University · CNZunyi Medical University · CN

Funding

National Natural Science Foundation of China 31571425, 81402970; 81402013
6 · The paper itself

Abstract

backgroundTriple-negative breast cancer (TNBC) is often aggressive and associated with a poor prognosis. Due to the lack of available targeted therapies and to problems of resistance with conventional chemotherapeutic agents, finding new treatments for TNBC remains a challenge and a better therapeutic strategy is urgently required.

methodsTNBC cells and xenograft mice were treated with a combination of chloroquine (CQ) and isorhamnetin (IH). Mitochondrial fission, apoptosis, and related signaling pathways were determined by flow cytometry, immunofluorescence, and related molecular biological techniques.

resultsThe inhibition of autophagy/mitophagy by CQ selectively enhances IH-induced mitochondrial fission and apoptosis in TNBC cells but not in estrogen-dependent breast cancer cells. These events were accompanied by mitochondrial translocation of Bax and the release of cytochrome c. Mechanistically, these effects were associated with oxidative stress-mediated phosphorylation of CaMKII (Thr286) and Drp1 (S616), and subsequent mitochondrial translocation of CaMKII and Drp1. The interruption of the CaMKII pathway by genetic approaches (e.g. CaMKII mutant or siRNA) attenuated combination-mediated mitochondrial fission and apoptosis. The combination of CQ/IH was a marked inhibitor tumor growth, inducing apoptosis in the TNBC xenograft mouse model in association with the activation of CaMKII and Drp1 (S616).

conclusionsOur study highlights the critical role of ROS-mediating CaMKII/Drp1 signaling in the regulation of mitochondrial fission and apoptosis induced by combination of CQ/IH. These findings also suggest that IH could potentially be further developed as a novel chemotherapeutic agent. Furthermore, a combination of IH with classic autophagy/mitophagy inhibitor could represent a novel therapeutic strategy for the treatment of TNBC.

Indexed as

AnimalsAntineoplastic Combined Chemotherapy ProtocolsCalcium-Calmodulin-Dependent Protein Kinase Type 2Cell Line, TumorCell ProliferationCell SurvivalChloroquineDynaminsFemaleGTP PhosphohydrolasesHumansMiceMicrotubule-Associated ProteinsMitochondrial DynamicsMitochondrial ProteinsQuercetin3-methylquercetinCalcium-Calmodulin-Dependent Protein Kinase Type 2ChloroquineDNM1L protein, humanDynaminsGTP PhosphohydrolasesMicrotubule-Associated ProteinsMitochondrial ProteinsQuercetinReactive Oxygen SpeciesApoptosisAutophagyCaMKIIChloroquineDrp1IsorhamnetinTriple-negative breast cancer

Identifiers

PMID31138329
PMCPMC6540563
OpenAlexW2947017356

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.