title: The expression of P-gp in leukemia cells is associated with cross-resistance to protein N-glycosylation inhibitor tunicamycin.
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.
authors.affiliation: Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Dubravska cesta 9, 840 05 Bratislava, Slovak Republic. zdena.sulova@savba.sk.
authors.forename: Lucia
authors.initials: L
authors.lastname: Pavlikova
authors.forename: Mario
authors.initials: M
authors.lastname: Seres
authors.forename: Denisa
authors.initials: D
authors.lastname: Imrichova
authors.forename: Milan
authors.initials: M
authors.lastname: Hano
authors.forename: Andrej
authors.initials: A
authors.lastname: Rusnak
authors.forename: Martina
authors.initials: M
authors.lastname: Zamorova
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Katrlik
authors.forename: Albert
authors.initials: A
authors.lastname: Breier
authors.forename: Zdena
authors.initials: Z
authors.lastname: Sulova
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome; D014415:Tunicamycin / Q000008:administration & dosage*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014415:Tunicamycin