ArticleMolecular pharmacology2012
Obatoclax and lapatinib interact to induce toxic autophagy through NOXA.
Article in Molecular pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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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.
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Who cites it
33 citing papers in PubMed, 56 citations in OpenAlex.
- Promoting reactive oxygen species accumulation to overcome tyrosine kinase inhibitor resistance in cancer.Cancer cell international · 2024Review
- Effect of natural products on host cell autophagy induced by Influenza A virus infection.Frontiers in cellular and infection microbiology · 2024Review
- Dietary Energy Modulation and Autophagy: Exploiting Metabolic Vulnerabilities to Starve Cancer.Frontiers in cell and developmental biology · 2020Review
- Crosstalk between let-7a-5p and BCL-xL in the Initiation of Toxic Autophagy in Lung Cancer.Molecular therapy oncolytics · 2019Article
- Glucose-6-phosphate dehydrogenase blockade potentiates tyrosine kinase inhibitor effect on breast cancer cells through autophagy perturbation.Journal of experimental & clinical cancer research : CR · 2019Article
- Obatoclax and Paclitaxel Synergistically Induce Apoptosis and Overcome Paclitaxel Resistance in Urothelial Cancer Cells.Cancers · 2018Article
- Novel imidazopyridine suppresses STAT3 activation by targeting SHP-1.Journal of enzyme inhibition and medicinal chemistry · 2018Article
- Review
- MDA-9/Syntenin regulates protective autophagy in anoikis-resistant glioma stem cells.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Article
- Review
- The tubulin inhibitor MG-2477 induces autophagy-regulated cell death, ROS accumulation and activation of FOXO3 in neuroblastoma.Oncotarget · 2017Article
- Article
- Obatoclax kills anaplastic thyroid cancer cells by inducing lysosome neutralization and necrosis.Oncotarget · 2016Article
- Obatoclax impairs lysosomal function to block autophagy in cisplatin-sensitive and -resistant esophageal cancer cells.Oncotarget · 2016Article
- Article
- Lapatinib induces autophagic cell death and differentiation in acute myeloblastic leukemia.OncoTargets and therapy · 2016Article
- Suppression of mTOR pathway and induction of autophagy-dependent cell death by cabergoline.Oncotarget · 2015Article
- Recent insights into cell death and autophagy.The FEBS journal · 2015Review
- Nexavar/Stivarga and viagra interact to kill tumor cells.Journal of cellular physiology · 2015Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Prior studies demonstrated that resistance to the ERBB1/2 inhibitor lapatinib could be overcome by the B cell CLL/lymphoma-2 (BCL-2) family antagonist obatoclax (GX15-070). Coadministration of lapatinib with obatoclax caused synergistic cell killing by eliciting autophagic cell death that was dependent upstream on mitochondrial reactive oxygen species generation and increased p62 levels and downstream on activation of p38 mitogen-activated protein kinase and inactivation of mammalian target of rapamycin. By immunohistochemical analysis, in drug combination-treated cells, microtubule-associated protein light chain 3 (LC3) associated with mitochondrial (cytochrome c oxidase), autophagosome (p62), and autolysosome (lysosomal associated membrane protein 2) proteins. Treatment of cells with 3-methyladenine or knockdown of beclin 1 was protective, whereas chloroquine treatment had no protective effect. Expression of myeloid cell leukemia-1 (MCL-1), compared with that of BCL-2 or BCL-2-related gene long isoform, protected against drug combination lethality. Lapatinib and obatoclax-initiated autophagy depended on NOXA-mediated displacement of the prosurvival BCL-2 family member, MCL-1, from beclin 1, which was essential for the initiation of autophagy. Taken together, our data argue that lapatinib and obatoclax-induced toxic autophagy is due to impaired autophagic degradation, and this disturbance of autophagic flux leads to an accumulation of toxic proteins and loss of mitochondrial function.
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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.