ArticleAutophagy2015
A novel autophagy/mitophagy inhibitor liensinine sensitizes breast cancer cells to chemotherapy through DNM1L-mediated mitochondrial fission.
Article in Autophagy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers.
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Who cites it
130 citing papers in PubMed, 249 citations in OpenAlex.
- Mitophagy coordinates organelle crosstalk in health and diseases.Signal transduction and targeted therapy · 2026Review
- Decoding Mitophagy in Breast Cancer: Biological Mechanisms, Dual Roles, and Clinical Implications.Cells · 2026Review
- Enhancing platinum-based chemotherapy efficacy and safety through combination therapy-mediated remodeling of autophagic homeostasis in gastric cancer.Cell death & disease · 2026Article
- The application of nanotechnology in regulating mitochondrial function in tumor microenvironment for cancer therapy.Theranostics · 2026Review
- Molecular mechanism and potential role of mitophagy in breast cancer.Journal of Cancer · 2026Review
- Therapeutic Promise of Mitophagy in Cancer: Advancing from Small-Molecule Regulation to Nanotechnology-Enhanced Targeting Therapy.Theranostics · 2026Review
- Comprehensive Evaluation of Usnic Acid as a Potential Drug Candidate for Triple-Negative Breast Cancer: Insights from Transcriptomic, Proteomic, and In Vivo Analyses.Molecules (Basel, Switzerland) · 2025Article
- Mortalin and PINK1/Parkin-Mediated Mitophagy Represent Ovarian Cancer-Selective Targets for Drug Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Mitochondrial Quality Control in Neurodegeneration and Cancer: A Common Denominator, Distinct Therapeutic Challenges.International journal of molecular sciences · 2025Review
- Mitophagy's impacts on cancer and neurodegenerative diseases: implications for future therapies.Journal of hematology & oncology · 2025Review
- Depleting chemoresponsive mitochondrial fission mediator DRP1 does not mitigate sarcoma resistance.Life science alliance · 2025Article
- Macranthoside B Suppresses the Growth of Adenocarcinoma of Esophagogastric Junction by Regulating Iron Homeostasis and Ferroptosis through NRF2 Inhibition.Current cancer drug targets · 2025Article
- Role of mitochondrial quality control in neurodegenerative disease progression.Frontiers in cellular neuroscience · 2025Review
- New insights into mitochondrial quality control in anthracycline-induced cardiotoxicity: molecular mechanisms, therapeutic targets, and natural products.International journal of biological sciences · 2025Review
- Autophagy in doxorubicin resistance: basic concepts, therapeutic perspectives and clinical translation.Frontiers in immunology · 2025Review
- A Mitochondria-Related Signature in Diffuse Large B-Cell Lymphoma: Prognosis, Immune and Therapeutic Features.Cancer medicine · 2025Article
- Natural autophagy modulators in non-communicable diseases: from autophagy mechanisms to therapeutic potential.Acta pharmacologica Sinica · 2025Review
- Role of mitophagy in breast cancer: mitophagy-apoptosis balance and reactive oxygen species play determining role.Frontiers in physiology · 2025Review
- Mitophagy: insights into its signaling molecules, biological functions, and therapeutic potential in breast cancer.Cell death discovery · 2024Review
- Thiostrepton as a Potential Therapeutic Agent for Hepatocellular Carcinoma.International journal of molecular sciences · 2024Article
70 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autophagy inhibition has been widely accepted as a promising therapeutic strategy in cancer, while the lack of effective and specific autophagy inhibitors hinders its application. Here we found that liensinine, a major isoquinoline alkaloid, inhibits late-stage autophagy/mitophagy through blocking autophagosome-lysosome fusion. This effect is likely achieved via inhibiting the recruitment of RAB7A to lysosomes but not to autophagosomes. We further investigated the effects of autophagy inhibition by liensinine on the therapeutic efficacy of chemotherapeutic drugs and found that cotreatment of liensinine markedly decreased the viability and increased apoptosis in breast cancer cells treated with various chemotherapeutic agents. Mechanistically, we found that inhibition of autophagy/mitophagy by liensinine enhanced doxorubicin-mediated apoptosis by triggering mitochondrial fission, which resulted from dephosphorylation and mitochondrial translocation of DNM1L. However, blocking autophagosome/mitophagosome formation by pharmacological or genetic approaches markedly attenuated mitochondrial fission and apoptosis in cells with combinatatorial treatment. Moreover, liensinine was synergized with doxorubicin to inhibit tumor growth in MDA-MB-231 xenograft in vivo. Our findings suggest that liensinine could potentially be further developed as a novel autophagy/mitophagy inhibitor, and a combination of liensinine with classical chemotherapeutic drugs could represent a novel therapeutic strategy for treatment of breast cancer.
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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.