{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:15:13Z","timestamp":1787505313055,"version":"build-2736575974"},"reference-count":67,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,4,20]],"date-time":"2021-04-20T00:00:00Z","timestamp":1618876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["DEC-2012\/05\/N\/NZ3\/01014"],"award-info":[{"award-number":["DEC-2012\/05\/N\/NZ3\/01014"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Chronic myeloid leukemia (CML) develops due to the presence of the BCR-ABL1 protein, a target of tyrosine kinase inhibitors (TKIs), such as imatinib (IM), used in a CML therapy. CML eradication is a challenge due to developing resistance to TKIs. BCR-ABL1 induces endogenous oxidative stress leading to genomic instability and development of TKI resistance. Model CML cells susceptible or resistant to IM, as well as wild-type, non-cancer cells without the BCR-ABL1 protein were treated with IM, hydrogen peroxide (H2O2) as a model trigger of external oxidative stress, or with IM+H2O2. Accumulation of reactive oxygen species (ROS), DNA damage, activity of selected antioxidant enzymes and glutathione (GSH), and mitochondrial potential (MMP) were assessed. We observed increase in ROS accumulation in BCR-ABL1 positive cells and distinct levels of ROS accumulation in IM-susceptible cells when compared to IM-resistant ones, as well as increased DNA damage caused by IM action in sensitive cells. Depletion of GSH levels and a decreased activity of glutathione peroxidase (GPx) in the presence of IM was higher in the cells susceptible to IM. IM-resistant cells showed an increase of catalase activity and a depletion of MMP. BCR-ABL1 kinase alters ROS metabolism, and IM resistance is accompanied by the changes in activity of GPx, catalase, and alterations in MMP.<\/jats:p>","DOI":"10.3390\/biom11040610","type":"journal-article","created":{"date-parts":[[2021,4,20]],"date-time":"2021-04-20T13:58:04Z","timestamp":1618927084000},"page":"610","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Relationship between Oxidative Stress and Imatinib Resistance in Model Chronic Myeloid Leukemia Cells"],"prefix":"10.3390","volume":"11","author":[{"given":"Sylwester","family":"G\u0142owacki","sequence":"first","affiliation":[{"name":"Laboratory of Medical Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141\/143 Street, 90-236 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewelina","family":"Synowiec","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141\/143 Street, 90-236 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2102-3741","authenticated-orcid":false,"given":"Marzena","family":"Szwed","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141\/143 Street, 90-236 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Toma","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141\/143 Street, 90-236 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Skorski","sequence":"additional","affiliation":[{"name":"Fels Cancer Institute for Personalized Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8385-7744","authenticated-orcid":false,"given":"Tomasz","family":"\u015aliwi\u0144ski","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141\/143 Street, 90-236 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4808","DOI":"10.1182\/blood-2008-07-077958","article-title":"Translation of the Philadelphia chromosome into therapy for CML","volume":"112","author":"Druker","year":"2008","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1038\/315550a0","article-title":"Fused transcript of abl and bcr genes in chronic myelogenous leukaemia","volume":"315","author":"Shtivelman","year":"1985","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/bs.acr.2018.02.003","article-title":"Acquired Resistance to Drugs Targeting Tyrosine Kinases","volume":"138","author":"Rosenzweig","year":"2018","journal-title":"Adv. Cancer Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/596483","article-title":"Therapy of Chronic Myeloid Leukemia: Twilight of the Imatinib Era?","volume":"2014","author":"Trela","year":"2014","journal-title":"ISRN Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s12943-018-0805-1","article-title":"Non ABL-directed inhibitors as alternative treatment strategies for chronic myeloid leukemia","volume":"17","author":"Massimino","year":"2018","journal-title":"Mol. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1097\/MOH.0000000000000403","article-title":"Resistance in chronic myeloid leukemia: Definitions and novel therapeutic agents","volume":"25","author":"Talati","year":"2018","journal-title":"Curr. Opin. Hematol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nrm2312","article-title":"Apoptosis: Controlled demolition at the cellular level","volume":"9","author":"Taylor","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.freeradbiomed.2009.12.022","article-title":"Reactive oxygen species, cellular redox systems, and apoptosis","volume":"48","author":"Circu","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1146\/annurev.pharmtox.47.120505.105122","article-title":"Mitochondrial oxidative stress: Implications for cell death","volume":"47","author":"Orrenius","year":"2007","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1038\/leu.2008.78","article-title":"BCR\/ABL promotes accumulation of chromosomal aberrations induced by oxidative and genotoxic stress","volume":"22","author":"Koptyra","year":"2008","journal-title":"Leukemia"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.bbrc.2017.06.190","article-title":"BCL-2 proteins and apoptosis: Recent insights and unknowns","volume":"500","author":"Edlich","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.bcp.2018.05.013","article-title":"Celecoxib inhibits mitochondrial O2 consumption, promoting ROS dependent death of murine and human metastatic cancer cells via the apoptotic signalling pathway","volume":"154","author":"Pritchard","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1080\/01635581.2018.1445769","article-title":"Piperlongumine Induces Apoptosis in Human Melanoma Cells Via Reactive Oxygen Species Mediated Mitochondria Disruption","volume":"70","author":"Song","year":"2018","journal-title":"Nutr. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1007\/s10495-017-1424-9","article-title":"Induction of reactive oxygen species: An emerging approach for cancer therapy","volume":"22","author":"Zou","year":"2017","journal-title":"Apoptosis"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.jcis.2016.01.012","article-title":"Exploitation of redox discrepancy in leukemia cells by a reactive oxygen species nanoscavenger for inducing cytotoxicity in imatinib resistant cells","volume":"467","author":"Acharya","year":"2016","journal-title":"J. Colloid Interface Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"673512","DOI":"10.1155\/2015\/673512","article-title":"Doxorubicin Differentially Induces Apoptosis, Expression of Mitochondrial Apoptosis-Related Genes, and Mitochondrial Potential in BCR-ABL1-Expressing Cells Sensitive and Resistant to Imatinib","volume":"2015","author":"Synowiec","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1016\/j.exphem.2016.08.008","article-title":"NOX-driven ROS formation in cell transformation of FLT3-ITD-positive AML","volume":"44","author":"Jayavelu","year":"2016","journal-title":"Exp. Hematol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/leu.2010.263","article-title":"NADPH oxidases regulate cell growth and migration in myeloid cells transformed by oncogenic tyrosine kinases","volume":"25","author":"Reddy","year":"2011","journal-title":"Leukemia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3433","DOI":"10.1002\/cncr.26621","article-title":"Inhibition of the NADPH oxidase regulates heme oxygenase 1 expression in chronic myeloid leukemia","volume":"118","author":"Singh","year":"2012","journal-title":"Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3173","DOI":"10.1182\/blood-2007-05-092510","article-title":"Internal tandem duplication of FLT3 (FLT3\/ITD) induces increased ROS production, DNA damage, and misrepair: Implications for poor prognosis in AML","volume":"111","author":"Sallmyr","year":"2008","journal-title":"Blood"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9348","DOI":"10.1074\/jbc.M113.510495","article-title":"NADPH oxidase-generated hydrogen peroxide induces DNA damage in mutant FLT3-expressing leukemia cells","volume":"290","author":"Stanicka","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"904","DOI":"10.2174\/1389557517666170228115324","article-title":"Reactive Oxygen and Nitrogen Species in Carcinogenesis: Implications of Oxidative Stress on the Progression and Development of Several Cancer Types","volume":"17","author":"Kruk","year":"2017","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1749-6632.2010.05608.x","article-title":"Role of oxidative\/nitrosative stress-mediated Bcl-2 regulation in apoptosis and malignant transformation","volume":"1203","author":"Azad","year":"2010","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1038\/leu.2014.245","article-title":"Combined STAT3 and BCR-ABL1 inhibition induces synthetic lethality in therapy-resistant chronic myeloid leukemia","volume":"29","author":"Eiring","year":"2015","journal-title":"Leukemia"},{"key":"ref_25","first-page":"1","article-title":"Reactive oxygen species in BCR-ABL1-expressing cells-relevance to chronic myeloid leukemia","volume":"64","author":"Pawlowska","year":"2017","journal-title":"Acta Biochim. Pol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1084\/jem.189.8.1229","article-title":"Signal transducer and activator of transcription (STAT)5 activation by BCR\/ABL is dependent on intact Src homology (SH)3 and SH2 domains of BCR\/ABL and is required for leukemogenesis","volume":"189","author":"Wasik","year":"1999","journal-title":"J. Exp. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4189","DOI":"10.1128\/MCB.22.12.4189-4201.2002","article-title":"Fusion tyrosine kinases induce drug resistance by stimulation of homology-dependent recombination repair, prolongation of G(2)\/M phase, and protection from apoptosis","volume":"22","author":"Slupianek","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/0014-4827(88)90265-0","article-title":"A simple technique for quantitation of low levels of DNA damage in individual cells","volume":"175","author":"Singh","year":"1988","journal-title":"Exp. Cell Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/jid.1967.24","article-title":"The measurement of glutathione in human epidermis using glutathione reductase","volume":"48","author":"Halprin","year":"1967","journal-title":"J. Investig. Dermatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3289","DOI":"10.1016\/j.bbagen.2012.11.020","article-title":"Glutathione peroxidases","volume":"1830","author":"Maiorino","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_31","first-page":"287","article-title":"First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid","volume":"54","author":"Ighodaro","year":"2018","journal-title":"Alex. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"18111","DOI":"10.3390\/ijms160818111","article-title":"UV Differentially Induces Oxidative Stress, DNA Damage and Apoptosis in BCR-ABL1-Positive Cells Sensitive and Resistant to Imatinib","volume":"16","author":"Synowiec","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1038\/sj.clpt.6100268","article-title":"Expression of the uptake drug transporter hOCT1 is an important clinical determinant of the response to imatinib in chronic myeloid leukemia","volume":"83","author":"Wang","year":"2008","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.25083\/rbl\/25.1\/1267.1274","article-title":"The involvement of oxidative stress in Chronic Myeloid Leukemia","volume":"25","author":"Pascu","year":"2020","journal-title":"Rom. Biotechnol. Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1182\/blood-2005-07-2815","article-title":"BCR\/ABL kinase induces self-mutagenesis via reactive oxygen species to encode imatinib resistance","volume":"108","author":"Koptyra","year":"2006","journal-title":"Blood"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1097\/CAD.0b013e3283140c6f","article-title":"Modulation of reactive oxygen species by antioxidants in chronic myeloid leukemia cells enhances imatinib sensitivity through survivin downregulation","volume":"19","author":"Kwee","year":"2008","journal-title":"Anticancer Drugs"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1182\/blood-2004-03-0849","article-title":"Activation of the PI3K\/mTOR pathway by BCR-ABL contributes to increased production of reactive oxygen species","volume":"105","author":"Kim","year":"2005","journal-title":"Blood"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1089\/biores.2015.0022","article-title":"Reactive Oxygen Species and Mitochondrial DNA Damage and Repair in BCR-ABL1 Cells Resistant to Imatinib","volume":"4","author":"Blasiak","year":"2015","journal-title":"BioRes. Open Access"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3193","DOI":"10.37358\/RC.19.9.7514","article-title":"Oxidative stress and BCR-ABL1 transcript levels in chronic myeloid leukemia: An intricate relationship","volume":"70","author":"Pascu","year":"2019","journal-title":"Rev. Chim."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.3109\/10428194.2016.1142086","article-title":"Metabolic characterization of imatinib-resistant BCR-ABL T315I chronic myeloid leukemia cells indicates down-regulation of glycolytic pathway and low ROS production","volume":"57","author":"Ko","year":"2016","journal-title":"Leuk. Lymphoma"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1038\/nrd2803","article-title":"Targeting cancer cells by ROS-mediated mechanisms: A radical therapeutic approach?","volume":"8","author":"Trachootham","year":"2009","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1186\/s13046-018-0909-x","article-title":"The role of cellular reactive oxygen species in cancer chemotherapy","volume":"37","author":"Yang","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/S0891-5849(02)01005-5","article-title":"Redox signaling in vascular angiogenesis","volume":"33","author":"Maulik","year":"2002","journal-title":"Free Radic. Biol. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1089\/152308603770380089","article-title":"Oxidants in receptor tyrosine kinase signal transduction pathways","volume":"5","author":"Aslan","year":"2003","journal-title":"Antioxid. Redox Signal."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/s13046-018-0797-0","article-title":"Reactive oxygen species in haematopoiesis: Leukaemic cells take a walk on the wild side","volume":"37","author":"Ijurko","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.yjmcc.2014.01.018","article-title":"An overview of mechanisms of redox signaling","volume":"73","author":"Forman","year":"2014","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1016\/j.fct.2007.04.003","article-title":"Cytoprotective effect of anthocyanins against doxorubicin-induced toxicity in H9c2 cardiomyocytes in relation to their antioxidant activities","volume":"45","author":"Choi","year":"2007","journal-title":"Food Chem. Toxicol."},{"key":"ref_48","first-page":"303","article-title":"Role of glutathione in cancer pathophysiology and therapeutic interventions","volume":"9","author":"Singh","year":"2012","journal-title":"J. Exp. Ther. Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1200\/JCO.2005.02.7110","article-title":"Role of the glutathione metabolic pathway in lung cancer treatment and prognosis: A review","volume":"24","author":"Yang","year":"2006","journal-title":"J. Clin. Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1002\/cbf.1149","article-title":"The role of glutathione in cancer","volume":"22","author":"Balendiran","year":"2004","journal-title":"Cell Biochem. Funct."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e3067","DOI":"10.1038\/cddis.2017.412","article-title":"Targeting redox homeostasis in rhabdomyosarcoma cells: GSH-depleting agents enhance auranofin-induced cell death","volume":"8","author":"Habermann","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.canlet.2019.11.040","article-title":"Preclinical development of a novel BCR-ABL T315I inhibitor against chronic myeloid leukemia","volume":"472","author":"Gupta","year":"2020","journal-title":"Cancer Lett."},{"key":"ref_53","first-page":"6450","article-title":"GPX3 promoter is methylated in chronic myeloid leukemia","volume":"8","author":"Yao","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1159\/000226487","article-title":"Reversal of human myeloid leukemia cells into normal granulocytes and macrophages: Activity and intracellular distribution of catalase","volume":"44","author":"Kos","year":"1987","journal-title":"Oncology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"21411","DOI":"10.1074\/jbc.M110.103564","article-title":"The in vivo toxicity of hydroxyurea depends on its direct target catalase","volume":"285","author":"Juul","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.2174\/092986709788186057","article-title":"In situ modulation of oxidative stress: A novel and efficient strategy to kill cancer cells","volume":"16","author":"Verrax","year":"2009","journal-title":"Curr. Med. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1007\/s10637-010-9441-3","article-title":"Ascorbate\/menadione-induced oxidative stress kills cancer cells that express normal or mutated forms of the oncogenic protein Bcr-Abl. An in vitro and in vivo mechanistic study","volume":"29","author":"Beck","year":"2011","journal-title":"Investig. New Drugs"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Song, L.-L., Tu, Y.-Y., Xia, L., Wang, W.-W., Wei, W., Ma, C.-M., Wen, D.-H., Lei, H., Xu, H.-Z., and Wu, Y.-L. (2014). Targeting catalase but not peroxiredoxins enhances arsenic trioxide-induced apoptosis in K562 cells. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0104985"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1080\/10428190802353617","article-title":"Catalase activity and arsenic sensitivity in acute leukemia","volume":"49","author":"Coe","year":"2008","journal-title":"Leuk. Lymphoma"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1080\/01635581.2018.1380208","article-title":"Synergistic Induction of Apoptosis by Quercetin and Curcumin in Chronic Myeloid Leukemia (K562) Cells","volume":"70","author":"Taga","year":"2018","journal-title":"Nutr. Cancer"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"28906","DOI":"10.18632\/oncotarget.15957","article-title":"Stellettin B induces apoptosis in human chronic myeloid leukemia cells via targeting PI3K and Stat5","volume":"8","author":"Chen","year":"2017","journal-title":"Oncotarget"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3348","DOI":"10.1182\/blood-2007-10-116236","article-title":"Effective dasatinib uptake may occur without human organic cation transporter 1 (hOCT1): Implications for the treatment of imatinib-resistant chronic myeloid leukemia","volume":"112","author":"Giannoudis","year":"2008","journal-title":"Blood"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3739","DOI":"10.1182\/blood-2003-12-4276","article-title":"Active transport of imatinib into and out of cells: Implications for drug resistance","volume":"104","author":"Thomas","year":"2004","journal-title":"Blood"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/sj.bjp.0706556","article-title":"Mitochondria: A target for cancer therapy","volume":"147","author":"Armstrong","year":"2006","journal-title":"Br. J. Pharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"526","DOI":"10.7326\/0003-4819-107-4-526","article-title":"Oxygen radicals and human disease","volume":"107","author":"Cross","year":"1987","journal-title":"Ann. Intern. Med."},{"key":"ref_66","first-page":"3246","article-title":"Suppression of KATP channel activity protects murine pancreatic beta cells against oxidative stress","volume":"119","author":"Gier","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1158\/1940-6207.CAPR-10-0326","article-title":"Mitochondrial subversion in cancer","volume":"4","author":"Chatterjee","year":"2011","journal-title":"Cancer Prev. Res."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/4\/610\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:50:12Z","timestamp":1760161812000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/4\/610"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,20]]},"references-count":67,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["biom11040610"],"URL":"https:\/\/doi.org\/10.3390\/biom11040610","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,20]]}}}