Home HOME General Physiology and Biophysics 2016 General Physiology and Biophysics Vol.35, No.4, p.497–510, 2016

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Quarterly, 80 pp. per issue
Founded: 1982
ISSN  1338-4325 (online)

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General Physiology and Biophysics Vol.35, No.4, p.497–510, 2016

Title: The expression of P-gp in leukemia cells is associated with cross-resistance to protein N-glycosylation inhibitor tunicamycin
Author: Lucia Pavlikova, Mario Seres, Denisa Imrichova, Milan Hano, Andrej Rusnak, Martina Zamorova, Jaroslav Katrlik, Albert Breier, Zdena Sulova
Abstract: 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.
Keywords: Leukemia cell lines — P-glycoprotein — Tunicamycin resistance — Apoptosis/necrosis detection — Lectins — Cell surface sugars
Published online: 06-Oct-2016
Year: 2016, Volume: 35, Issue: 4 Page From: 497, Page To: 510
doi:10.4149/gpb_2016039


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