Inhibition of Autophagy Does Not Re-Sensitize Acute Myeloid Leukemia Cells Resistant to Cytarabine
| العنوان: | Inhibition of Autophagy Does Not Re-Sensitize Acute Myeloid Leukemia Cells Resistant to Cytarabine |
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| المؤلفون: | Edwin Bremer, Nienke Visser, Valerie R. Wiersma, Gerwin Huls, Harm Jan Lourens |
| المساهمون: | Stem Cell Aging Leukemia and Lymphoma (SALL), Guided Treatment in Optimal Selected Cancer Patients (GUTS) |
| المصدر: | International Journal of Molecular Sciences Volume 22 Issue 5 International Journal of Molecular Sciences, 22(5):2337. MDPI AG International Journal of Molecular Sciences, Vol 22, Iss 2337, p 2337 (2021) |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Myeloid, Antimetabolites, Drug Resistance, Drug Resistance, Neoplasm/drug effects, lcsh:Chemistry, chloroquine, 0302 clinical medicine, AML, cytarabine, Neoplasm/drug effects, hemic and lymphatic diseases, Autophagy/drug effects, Tumor Cells, Cultured, Cytotoxic T cell, lcsh:QH301-705.5, Spectroscopy, Tumor, Chloroquine/pharmacology, Leukemia, Cultured, Myeloid leukemia, General Medicine, Cytarabine/pharmacology, Computer Science Applications, Tumor Cells, Leukemia, Myeloid, Acute, 030220 oncology & carcinogenesis, autophagy inhibitors, medicine.drug, Programmed cell death, Antimetabolites, Antineoplastic, autophagy, therapy resistance, Leukemia, Myeloid, Acute/drug therapy, Catalysis, Article, Cell Line, Inorganic Chemistry, 03 medical and health sciences, Antimetabolites, Antineoplastic/pharmacology, Cell Line, Tumor, medicine, Humans, Acute/drug therapy, Viability assay, Physical and Theoretical Chemistry, Molecular Biology, Antineoplastic/pharmacology, business.industry, Organic Chemistry, Autophagy, carbohydrates (lipids), 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, Cell culture, Drug Resistance, Neoplasm, Cancer cell, Cancer research, Cytarabine, business |
| الوصف: | Elevated activation of the autophagy pathway is currently thought to be one of the survival mechanisms allowing therapy-resistant cancer cells to escape elimination, including for cytarabine (AraC)-resistant acute myeloid leukemia (AML) patients. Consequently, the use of autophagy inhibitors such as chloroquine (CQ) is being explored for the re-sensitization of AraC-resistant cells. In our study, no difference in the activity of the autophagy pathway was detected when comparing AraC-Res AML cell lines to parental AraC-sensitive AML cell lines. Furthermore, treatment with autophagy inhibitors CQ, 3-Methyladenine (3-MA), and bafilomycin A1 (BafA1) did not re-sensitize AraC-Res AML cell lines to AraC treatment. However, in parental AraC-sensitive AML cells, treatment with AraC did activate autophagy and, correspondingly, combination of AraC with autophagy inhibitors strongly reduced cell viability. Notably, the combination of these drugs also yielded the highest level of cell death in a panel of patient-derived AML samples even though not being additive. Furthermore, there was no difference in the cytotoxic effect of autophagy inhibition during AraC treatment in matched de novo and relapse samples with differential sensitivity to AraC. Thus, inhibition of autophagy may improve AraC efficacy in AML patients, but does not seem warranted for the treatment of AML patients that have relapsed with AraC-resistant disease. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1422-0067 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4a50bf3f6211005f78ea9b457a2abd2c https://hdl.handle.net/11370/d64ada6f-7767-435f-af28-f4c0c8f01723 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....4a50bf3f6211005f78ea9b457a2abd2c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14220067 |
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