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.
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.
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Who cites it
87 citing papers in PubMed, 2 syntheses or guidelines pooled it, 138 citations in OpenAlex.
- Pooled it
- Roles of mitochondrial fusion and fission in breast cancer progression: a systematic review.World journal of surgical oncology · 2022Pooled it
- Mitochondrial dysfunction and oxidative stress in OSAHS and associated comorbidities: Mechanism and potential targeted therapeutic strategies.Redox biology · 2026Review
- Anticancer Potential of Cherry Extracts and Major Flavonols: Focus on Quercetin and Kaempferol Molecular Mechanisms in Breast Cancer.International journal of molecular sciences · 2026Review
- Multi-omic analysis of the liver-breast axis reveals key hepatic mediators of breast cancer progression.Science China. Life sciences · 2026Review
- Kisspeptin exacerbates androgen-induced follicular dysplasia by promoting Drp1 phosphorylation imbalance and mitochondrial excessive fission in granulosa cells of polycystic ovary syndrome.Journal of ovarian research · 2026Article
- Targeted Extracellular Vesicles Deliver Asiaticoside to Inhibit AURKB/DRP1-Mediated Mitochondrial Fission and Attenuate Hypertrophic Scar Formation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Neutrophil-initiated nociceptive ingrowth orchestrates inflammation resolution to potentiate bone regeneration.Bone research · 2026Article
- Progress in the antitumor molecular mechanisms of Isorhamnetin.Discover oncology · 2025Review
- Vesicle-mediated mitochondrial clearance presents an actionable metabolic vulnerability in triple-negative breast cancer.Cell reports. Medicine · 2025Article
- Urolithin Α modulates inter-organellar communication via calcium-dependent mitophagy to promote healthy ageing.Autophagy · 2025Article
- The role and application potential of cytochrome c in breast cancer therapy.Discover oncology · 2025Review
- Autophagy-Related Proteins in Triple-Negative Breast Cancer: From Molecular Insights to Therapeutic Applications.International journal of molecular sciences · 2025Review
- Precision therapy targeting CAMK2 to overcome resistance to EGFR inhibitors in FAT1 -mutated oral squamous cell carcinoma.Chinese medical journal · 2025Article
- Cigarette Tar Enhanced ECs Pyroptosis via CAMKII/Drp1/mtDNA: Novel Insight Into the Mechanism of Plaque Erosion.JACC. Basic to translational science · 2025Article
- Isorhamnetin: Reviewing Recent Developments in Anticancer Mechanisms and Nanoformulation-Driven Delivery.International journal of molecular sciences · 2025Review
- Research on mammary gland hyperplasia compound patents' herbal combination rules based on complex system entropy clustering: A review.Medicine · 2025Review
- ER-mitochondria tethering and its signaling: A novel therapeutic target in breast cancer.Molecular therapy. Oncology · 2025Review
- Advances in Isorhamnetin Treatment of Malignant Tumors: Mechanisms and Applications.Nutrients · 2025Review
- Isorhamnetin inhibits cholangiocarcinoma proliferation and metastasis via PI3K/AKT signaling pathway.Discover oncology · 2025Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
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.
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Registered trials
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.