ArticleScientific reports2016
Identification of Doxorubicin as an Inhibitor of the IRE1α-XBP1 Axis of the Unfolded Protein Response.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 34 citations in OpenAlex.
- Regulatory Mechanisms of XBP1 in Tumorigenesis and Cancer Progression: Challenges and Therapeutic Strategies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Organelle-Targeted Nanocarriers for Cancer Therapy: Design Principles, Intracellular Trafficking, and Translational Barriers in Precision Drug Delivery.International journal of nanomedicine · 2026Review
- Nerofe+ldDox releases c-Jun from nuclear ST2 to reprogram the immune microenvironment in mtKRAS tumors.Oncotarget · 2025Article
- Non-genetic inactivation of caspase-3 and P53 increases cancer cell fitness by PDIA4 redistribution.Oncogene · 2025Article
- Chemotherapy-Induced Cell-Surface GRP78 Expression as a Prognostic Marker for Invasiveness of Metastatic Triple-Negative Breast Cancer.Annals of biomedical engineering · 2025Article
- Recent advances in nanomedicine design strategies for targeting subcellular structures.iScience · 2025Review
- IRE1α determines ferroptosis sensitivity through regulation of glutathione synthesis.Nature communications · 2024Article
- Dual RNase activity of IRE1 as a target for anticancer therapies.Journal of cell communication and signaling · 2023Review
- Transformation of immunosuppressive mtKRAS tumors into immunostimulatory tumors by Nerofe and Doxorubicin.Oncotarget · 2023Article
- Cell surface GRP78: a potential mechanism of therapeutic resistant tumors.Cancer cell international · 2023Review
- Discovery of toxoflavin, a potent IRE1α inhibitor acting through structure-dependent oxidative inhibition.Acta pharmacologica Sinica · 2023Article
- Endoplasmic reticulum stress targeted therapy for breast cancer.Cell communication and signaling : CCS · 2022Review
- Doxorubicin-Induced TrkAIII Activation: A Selection Mechanism for Resistant Dormant Neuroblastoma Cells.International journal of molecular sciences · 2022Article
- Biological pathways and comparison with biopsy signals and cellular origin of peripheral blood transcriptomic profiles during kidney allograft pathology.Kidney international · 2022Article
- ATF6 prevents DNA damage and cell death in colon cancer cells undergoing ER stress.Cell death discovery · 2022Article
- Interconnected Adaptive Responses: A Way Out for Cancer Cells to Avoid Cellular Demise.Cancers · 2022Review
- Inhibition of mitochondrial complex III or dihydroorotate dehydrogenase (DHODH) triggers formation of poly(A)RNA biology · 2022Article
- Autophagic Organelles in DNA Damage Response.Frontiers in cell and developmental biology · 2021Review
- Endoplasmic Reticulum Stress Provocation by Different Nanoparticles: An Innovative Approach to Manage the Cancer and Other Common Diseases.Molecules (Basel, Switzerland) · 2020Review
- Inducing endoplasmic reticulum stress in cancer cells using graphene oxide-based nanoparticles.Nanoscale advances · 2020Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Activation of the IRE1α-XBP1 branch of the unfolded protein response (UPR) has been implicated in multiple types of human cancers, including multiple myeloma (MM). Through an in silico drug discovery approach based on protein-compound virtual docking, we identified the anthracycline antibiotic doxorubicin as an in vitro and in vivo inhibitor of XBP1 activation, a previously unknown activity for this widely utilized cancer chemotherapeutic drug. Through a series of mechanistic and phenotypic studies, we showed that this novel activity of doxorubicin was not due to inhibition of topoisomerase II (Topo II). Consistent with its inhibitory activity on the IRE1α-XBP1 branch of the UPR, doxorubicin displayed more potent cytotoxicity against MM cell lines than other cancer cell lines that have lower basal IRE1α-XBP1 activity. In addition, doxorubicin significantly inhibited XBP1 activation in CD138(+) tumor cells isolated from MM patients. Our findings suggest that the UPR-modulating activity of doxorubicin may be utilized clinically to target IRE1α-XBP1-dependent tumors such as MM.
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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.