The expression of P-gp in leukemia cells is associated with cross-resistance to protein N-glycosylation inhibitor tunicamycin
| Autor: | Albert Breier, Mário Šereš, Andrej Rusnak, Jaroslav Katrlík, Milan Hano, Martina Zámorová, Zdena Sulova, Denisa Imrichova, Lucia Pavlikova |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Vincristine Glycosylation Physiology Biophysics Apoptosis Biology 03 medical and health sciences chemistry.chemical_compound Cell Line Tumor medicine Humans ATP Binding Cassette Transporter Subfamily B Member 1 Leukemia Dose-Response Relationship Drug Tunicamycin Myeloid leukemia General Medicine Transfection Cell cycle medicine.disease Virology Molecular biology Treatment Outcome 030104 developmental biology chemistry Drug Resistance Neoplasm L1210 cells medicine.drug |
| Zdroj: | General physiology and biophysics. 35:497-510 |
| ISSN: | 1338-4325 |
| DOI: | 10.4149/gpb_2016039 |
| Popis: | In P-gp-positive cell variants obtained from L1210 cells either by selection with vincristine (L1210/R) or by transfection with the human gene encoding P-gp (L1210/T), we have previously described cross-resistance to tunicamycin (TNM), a protein N-glycosylation inhibitor. Here we studied whether this cross-resistance also underlies P-gp-positive variants of human acute myeloid leukemia cells (AML) derived from SKM-1 and MOLM-13 cells (SKM-1/VCR, SKM-1/LEN, MOLM-13/VCR) by selection with vincristine (VCR) and lenalidomide (LEN). While SKM-1/LEN cells were P-gp positive, no P-gp was detected in MOLM-13/LEN cells. P-gp-positive cells could be repeatedly passaged in medium containing TNM. In contrast, more than 90% of P-gp-negative cells were entering and progressing through cell death mechanisms after the third passage in medium containing TNM. Combined apoptosis/necrosis cell death was detected in L1210 cells after exposure to TNM. Passaging of P-gp-negative AML cells in medium containing TNM induced preferentially apoptosis. Damage to P-gp-negative cells induced with TNM was associated with arrest in the G1 phase of the cell cycle. P-gp-positive leukemia cells differed from P-gp-negative cells in the composition of plasma membrane glycoproteins, which we monitored with the aid of different lectins. The application of TNM to cells induced additional changes in membrane-linked glycosides. |
| Databáze: | OpenAIRE |
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