ArticleMolecules (Basel, Switzerland)2014
Nilotinib enhances the efficacy of conventional chemotherapeutic drugs in CD34⁺CD38⁻ stem cells and ABC transporter overexpressing leukemia cells.
Article in Molecules (Basel, Switzerland), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Article
- In vitro and ex vivo anti‑tumor effect and mechanism of Tucatinib in leukemia stem cells and ABCG2‑overexpressing leukemia cells.Oncology reports · 2021Article
- Clinical Relevance of ABCB1, ABCG2, and ABCC2 Gene Polymorphisms in Chronic Myeloid Leukemia Patients Treated With Nilotinib.Frontiers in oncology · 2021Article
- KD025, an anti-adipocyte differentiation drug, enhances the efficacy of conventional chemotherapeutic drugs in ABCG2-overexpressing leukemia cells.Oncology letters · 2020Article
- MicroRNA‑145 promotes the apoptosis of leukemic stem cells and enhances drug‑resistant K562/ADM cell sensitivity to adriamycin via the regulation of ABCE1.International journal of molecular medicine · 2020Article
- Towards Comprehension of the ABCB1/P-Glycoprotein Role in Chronic Myeloid Leukemia.Molecules (Basel, Switzerland) · 2018Review
- Characteristics of doxorubicin-selected multidrug-resistant human leukemia HL-60 cells with tolerance to arsenic trioxide and contribution of leukemia stem cells.Oncology letters · 2018Article
- Identification of OAT1/OAT3 as Contributors to Cisplatin Toxicity.Clinical and translational science · 2017Article
- Overexpression of lncRNA NEAT1 mitigates multidrug resistance by inhibiting ABCG2 in leukemia.Oncology letters · 2016Article
- Pharmacogenetics of BCR/ABL Inhibitors in Chronic Myeloid Leukemia.International journal of molecular sciences · 2015Review
- Sp1 and c-Myc modulate drug resistance of leukemia stem cells by regulating survivin expression through the ERK-MSK MAPK signaling pathway.Molecular cancer · 2015Article
- Papillary renal cell carcinoma: a clinicopathological and whole-genome exon sequencing study.International journal of clinical and experimental pathology · 2015Article
- Lapatinib antagonizes multidrug resistance-associated protein 1-mediated multidrug resistance by inhibiting its transport function.Molecular medicine (Cambridge, Mass.) · 2014Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Incomplete chemotherapeutic eradication of leukemic CD34⁺CD38⁻ stem cells is likely to result in disease relapse. The purpose of this study was to evaluate the effect of nilotinib on eradicating leukemia stem cells and enhancing the efficacy of chemotherapeutic agents. Our results showed that ABCB1 and ABCG2 were preferentially expressed in leukemic CD34⁺CD38⁻ cells. Nilotinib significantly enhanced the cytotoxicity of doxorubicin and mitoxantrone in CD34⁺CD38⁻ cells and led to increased apoptosis. Moreover, nilotinib strongly reversed multidrug resistance and increased the intracellular accumulation of rhodamine 123 in primary leukemic blasts overexpressing ABCB1 and/or ABCG2. Studies with ABC transporter-overexpressing carcinoma cell models confirmed that nilotinib effectively reversed ABCB1- and ABCG2-mediated drug resistance, while showed no significant reversal effect on ABCC1- and ABCC4-mediated drug resistance. Results from cytotoxicity assays showed that CD34⁺CD38⁻ cells exhibited moderate resistance (2.41-fold) to nilotinib, compared with parental K562 cells. Furthermore, nilotinib was less effective in blocking the phosphorylation of Bcr-Abl and CrkL (a substrate of Bcr-Abl kinase) in CD34⁺CD38⁻ cells. Taken together, these data suggest that nilotinib particularly targets CD34⁺CD38⁻ stem cells and MDR leukemia cells, and effectively enhances the efficacy of chemotherapeutic drugs by blocking the efflux function of ABC transporters.
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