Open AccessSchizandrol A reverses multidrug resistance in resistant chronic myeloid leukemia cells K562/A02
Author(s) -
Nurguli Arken
Publication year - 2019
Publication title -
cellular and molecular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.371
H-Index - 71
eISSN - 1165-158X
pISSN - 0145-5680
DOI - 10.14715/cmb/2019.65.1.14
Subject(s) - multiple drug resistance , myeloid leukemia , k562 cells , efflux , pharmacology , biology , cytotoxic t cell , drug resistance , cytotoxicity , pi3k/akt/mtor pathway , protein kinase b , leukemia , cancer research , in vitro , immunology , biochemistry , signal transduction , microbiology and biotechnology
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.