lignans and Leukemia--Myelogenous--Chronic--BCR-ABL-Positive

Overexpression of P-gp is the main cause of multidrug resistance (MDR) and chemotherapeutic failure in leukemia. In this study, the multidrug resistance reverse effect of Schizandrol A (SchA) was demonstrated with P-gp overexpressed drug-resistant K562/A02 cells. SchA had almost no cytotoxic activity, the EC50 value reversed to DOX was in the nanomole range of (707 ± 29nM) and had a high selectivity index (> 113) to normal cells. DOX accumulation and Rh123 efflux tests demonstrated that the MDR reversal activity of SchA was induced by inhibiting P-gp function. Western blotting assay showed that SchA down-regulated the expression of P-gp by inhibiting the PI3K / Akt signaling pathway, which was also a key factor in reversal activity. Therefore, SchA may be a potential candidate for natural MDR reversal agents.

Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Cell Death; Cyclooctanes; Doxorubicin; Drug Resistance, Neoplasm; Humans; Intracellular Space; K562 Cells; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lignans; Phosphorylation; Polycyclic Compounds; Proto-Oncogene Proteins c-akt; Rhodamine 123