ArticleCancer science2009
Dofequidar fumarate sensitizes cancer stem-like side population cells to chemotherapeutic drugs by inhibiting ABCG2/BCRP-mediated drug export.
Article in Cancer science, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 73 citations in OpenAlex.
- Cancer-associated fibroblasts and prostate cancer stem cells: crosstalk mechanisms and implications for disease progression.Frontiers in cell and developmental biology · 2024Review
- Fibroblast growth factor receptor 3 overexpression mediates ALK inhibitor resistance in ALK-rearranged non-small cell lung cancer.Cancer science · 2022Article
- Drug and apoptosis resistance in cancer stem cells: a puzzle with many pieces.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Reporters of Cancer Stem Cells as a Tool for Drug Discovery.Frontiers in oncology · 2021Review
- Cancer stem cells and oral cancer: insights into molecular mechanisms and therapeutic approaches.Cancer cell international · 2020Review
- The Role of Breast Cancer Stem Cells as a Prognostic Marker and a Target to Improve the Efficacy of Breast Cancer Therapy.Cancers · 2019Review
- Review
- Cell Migration Related to MDR-Another Impediment to Effective Chemotherapy?Molecules (Basel, Switzerland) · 2018Review
- RNA-binding motif protein 47 inhibits Nrf2 activity to suppress tumor growth in lung adenocarcinoma.Oncogene · 2016Article
- P-glycoprotein Mediates Ceritinib Resistance in Anaplastic Lymphoma Kinase-rearranged Non-small Cell Lung Cancer.EBioMedicine · 2016Article
- Targeting Head and Neck Cancer Stem Cells: Current Advances and Future Challenges.Journal of dental research · 2015Review
- Different Effects of BORIS/CTCFL on Stemness Gene Expression, Sphere Formation and Cell Survival in Epithelial Cancer Stem Cells.PloS one · 2015Article
- Omega-3 fatty acid is a potential preventive agent for recurrent colon cancer.Cancer prevention research (Philadelphia, Pa.) · 2014Article
- Human ABC transporter ABCG2/BCRP expression in chemoresistance: basic and clinical perspectives for molecular cancer therapeutics.Pharmacogenomics and personalized medicine · 2014Review
- Reversal of multidrug resistance by the anti-malaria drug artesunate in the esophageal cancer Eca109/ABCG2 cell line.Oncology letters · 2013Article
- The effect of breast cancer resistance protein, multidrug resistant protein 1, and organic anion-transporting polypeptide 1B3 on the antitumor efficacy of the lipophilic camptothecin 7-t-butyldimethylsilyl-10-hydroxycamptothecin (AR-67) in vitro.Drug metabolism and disposition: the biological fate of chemicals · 2013Article
- Emodin as an effective agent in targeting cancer stem-like side population cells of gallbladder carcinoma.Stem cells and development · 2013Article
- Side population cells as prototype of chemoresistant, tumor-initiating cells.BioMed research international · 2013Review
- Axitinib targeted cancer stemlike cells to enhance efficacy of chemotherapeutic drugs via inhibiting the drug transport function of ABCG2.Molecular medicine (Cambridge, Mass.) · 2012Article
- Role of breast cancer resistance protein (BCRP/ABCG2) in cancer drug resistance.Biochemical pharmacology · 2012Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ATP-binding cassette (ABC) transporters (ABC-T) actively efflux structurally and mechanistically unrelated anticancer drugs from cells. As a consequence, they can confer multidrug resistance (MDR) to cancer cells. ABC-T are also reported to be phenotypic markers and functional regulators of cancer stem/initiating cells (CSC) and believed to be associated with tumor initiation, progression, and relapse. Dofequidar fumarate, an orally active quinoline compound, has been reported to overcome MDR by inhibiting ABCB1/P-gp, ABCC1/MDR-associated protein 1, or both. Phase III clinical trials suggested that dofequidar had efficacy in patients who had not received prior therapy. Here we show that dofequidar inhibits the efflux of chemotherapeutic drugs and increases the sensitivity to anticancer drugs in CSC-like side population (SP) cells isolated from various cancer cell lines. Dofequidar treatment greatly reduced the cell number in the SP fraction. Estimation of ABC-T expression revealed that ABCG2/breast cancer resistance protein (BCRP) mRNA level, but not the ABCB1/P-gp or ABCC1/MDR-associated protein 1 mRNA level, in all the tested SP cells was higher than that in non-SP cells. The in vitro vesicle transporter assay clarified that dofequidar had the ability to suppress ABCG2/BCRP function. Dofequidar treatment sensitized SP cells to anticancer agents in vitro. We compared the antitumor efficacy of irinotecan (CPT-11) alone with that of CPT-11 plus dofequidar in xenografted SP cells. Although xenografted SP tumors showed resistance to CPT-11, treatment with CPT-11 plus dofequidar greatly reduced the SP-derived tumor growth in vivo. Our results suggest the possibility of selective eradication of CSC by inhibiting ABCG2/BCRP.
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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.