Spontaneous mitochondrial membrane potential change during apoptotic induction by quercetin in K562 and K562/adr cells

Abstract

Natural products from plants such as flavonoids are potential drugs to overcome multidrug resistance (MDR) in cancer treatments. However, their modes of action are still unclear. In this study, the effects of quercetin on mitochondrial membrane potential (DeltaPsim) change as well as quercetin's ability to induce apoptosis and inhibit Pgp-mediated efflux of 99mTc-MIBI in K562/adr cells were investigated. Quercetin exhibits cytotoxicity against erythroleukemic cells: IC50 are 11.0 +/- 2.0 micromol/L and 5.0 +/- 0.4 micromol/L for K562 and K562/adr, respectively. Quercetin induces cell death via apoptosis in both K562 and K562/adr cells and does not inhibit Pgp-mediated efflux of 99mTc-MIBI. Quercetin (10 micromol/L, 3 h) and etoposide (100 micromol/L, 24 h) induce similar levels of apoptosis in K562 and K562/adr cells. Quercetin induces an increase followed by a decrease in |DeltaPsim| value depending on its concentration. A decrease in the |DeltaPsim| value is associated with an increase in the percentage of early apoptotic cells. It is clearly shown that quercetin results in a spontaneous DeltaPsim change during apoptotic induction. Therefore, quercetin is potentially an apoptotic-inducing agent, which reacts at the mitochondrial level.

Quercetin: A potential drug to reverse multidrug resistance

“…HL60 (promyelocyte leukemia cells), K562(erythroleukemic cells), CCRF-CEM(T-lymphocytic leukemia cells) and their respective drug resistant counterparts HL60/VCR, K562/adr, CEM/ADR5000, CEM/VLB100 and CEM/E1000 (Duraj et al 2005;Kothan et al 2004;Efferth et al 2002). In addition, quercetin at a non-cytotoxic concentration has enhanced the effect of chemotherapeutic drug on MDR cells.…”

Tetrandrine prevents acquired drug resistance of K562 cells through inhibition of mdr1 gene transcription

“…Occurrence of acquired leukemia MDR was closely related to the overexpression of the multidrug resistance gene (mdr1) and its encoded protein, P-gp (Kothan et al 2004). Various exogenous stimuli can prompt mdr1 gene expression through diverse mechanisms.…”

Natural Products for Treatment of Chronic Myeloid Leukemia

“…Moreover, Q arrested CML cells at G2/M phase [83]. IC 50 of Q on K562 and K562/ADR was found to be 11 ± 2 μM and 5 ± 0.4 μM [84]. It also inhibited the Anti-cancer Drugs -Nature, Synthesis and Cell…”