ArticleProceedings of the National Academy of Sciences of the United States of America2012
Heat shock factor-1 knockout induces multidrug resistance gene, MDR1b, and enhances P-glycoprotein (ABCB1)-based drug extrusion in the heart.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 44 citations in OpenAlex.
- Nanoparticle-mediated magnetic hyperthermia in the treatment of neurological disorders.Nanomedicine (London, England) · 2025Review
- HSF1 at the crossroads of chemoresistance: from current insights to future horizons in cell death mechanisms.Frontiers in cell and developmental biology · 2024Review
- Exploring the effects of calycosin on anthracycline-induced cardiotoxicity: a network pharmacology, molecular docking, and experimental study.Frontiers in cardiovascular medicine · 2024Article
- KRIBB11 Induces Apoptosis in A172 Glioblastoma Cells via MULE-Dependent Degradation of MCL-1.Molecules (Basel, Switzerland) · 2021Article
- Heat Shock Proteins: Potential Modulators and Candidate Biomarkers of Peripartum Cardiomyopathy.Frontiers in cardiovascular medicine · 2021Review
- Shenmai injection suppresses multidrug resistance in MCF-7/ADR cells through the MAPK/NF-κB signalling pathway.Pharmaceutical biology · 2020Article
- Possible Susceptibility Genes for Intervention against Chemotherapy-Induced Cardiotoxicity.Oxidative medicine and cellular longevity · 2020Review
- Roles of heat shock factor 1 beyond the heat shock response.Cellular and molecular life sciences : CMLS · 2018Review
- Vitexin induces apoptosis by suppressing autophagy in multi-drug resistant colorectal cancer cells.Oncotarget · 2018Article
- The human amniotic fluid stem cell secretome effectively counteracts doxorubicin-induced cardiotoxicity.Scientific reports · 2016Article
- Heat shock factor-1 knockout enhances cholesterol 7α-hydroxylase (CYP7A1) and multidrug transporter (MDR1) gene expressions to attenuate atherosclerosis.Cardiovascular research · 2016Article
- Systems biology approaches to adverse drug effects: the example of cardio-oncology.Nature reviews. Clinical oncology · 2015Review
- Oestrogen enhances cardiotoxicity induced by Sunitinib by regulation of drug transport and metabolism.Cardiovascular research · 2015Article
- The tell-tale heart: molecular and cellular responses to childhood anthracycline exposure.American journal of physiology. Heart and circulatory physiology · 2014Review
- Pleiotropic role of HSF1 in neoplastic transformation.Current cancer drug targets · 2014Review
- Genomic profiling reveals the potential role of TCL1A and MDR1 deficiency in chemotherapy-induced cardiotoxicity.International journal of biological sciences · 2013Article
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Authors and funding
5 authors at 2 institutions in 1 country.
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Abstract
Heat-shock factor 1 (HSF-1), a transcription factor for heat-shock proteins (HSPs), is known to interfere with the transcriptional activity of many oncogenic factors. In the present work, we have discovered that HSF-1 ablation induced the multidrug resistance gene, MDR1b, in the heart and increased the expression of P-glycoprotein (P-gp, ABCB1), an ATP binding cassette that is usually associated with multidrug-resistant cancer cells. The increase in P-gp enhanced the extrusion of doxorubicin (Dox) to alleviate Dox-induced heart failure and reduce mortality in mice. Dox-induced left ventricular (LV) dysfunction was significantly reduced in HSF-1(-/-) mice. DNA-binding activity of NF-κB was higher in HSF-1(-/-) mice. IκB, the NF-κB inhibitor, was depleted due to enhanced IκB kinase (IKK)-α activity. In parallel, MDR1b gene expression and a large increase in P-gp and lowering Dox loading were observed in HSF-1(-/-) mouse hearts. Moreover, application of the P-gp antagonist, verapamil, increased Dox loading in HSF-1(-/-) cardiomyocytes, deteriorated cardiac function in HSF-1(-/-) mice, and decreased survival. MDR1 promoter activity was higher in HSF-1(-/-) cardiomyocytes, whereas a mutant MDR1 promoter with heat-shock element (HSE) mutation showed increased activity only in HSF-1(+/+) cardiomyocytes. However, deletion of HSE and NF-κB binding sites diminished luminescence in both HSF-1(+/+) and HSF-1(-/-) cardiomyocytes, suggesting that HSF-1 inhibits MDR1 activity in the heart. Thus, because high levels of HSF-1 are attributed to poor prognosis of cancer, systemic down-regulation of HSF-1 before chemotherapy is a potential therapeutic approach to ameliorate the chemotherapy-induced cardiotoxicity and enhance cancer prognosis.
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