Quercetin enhances adriamycin cytotoxicity through induction of apoptosis and regulation of mitogen‑activated protein kinase/extracellular signal‑regulated kinase/c‑Jun N‑terminal kinase signaling in multidrug‑resistant leukemia K562 cells

Chen,Fang‑Yuan; Cao,Lan‑Fang; Wan,Hai‑Xia; Zhang,Min‑Yue; Cai,Jia‑Yi; Shen,Li‑Jing; Zhong, Ji‑Hua; Zhong,Hua

doi:10.3892/mmr.2014.2734

Quercetin enhances adriamycin cytotoxicity through induction of apoptosis and regulation of mitogen‑activated protein kinase/extracellular signal‑regulated kinase/c‑Jun N‑terminal kinase signaling in multidrug‑resistant leukemia K562 cells

Authors:
- Fang‑Yuan Chen
- Lan‑Fang Cao
- Hai‑Xia Wan
- Min‑Yue Zhang
- Jia‑Yi Cai
- Li‑Jing Shen
- Ji‑Hua Zhong
- Hua Zhong
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Affiliations: Department of Hematology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China, Department of Pediatrics, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China
Published online on: October 21, 2014 https://doi.org/10.3892/mmr.2014.2734
Pages: 341-348

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Abstract

Multidrug resistance (MDR) has become a significant challenge in chemotherapeutic treatment of cancer. Quercetin, a naturally occurring flavonoid, has been found to possess anti‑proliferative, anti‑inflammatory and immunoregulatory bioactivities. The present study was performed to examine the effect of quercetin on human leukemic MDR K562/adriamycin (ADR) cells. Treatment of K562/ADR cells with a combination of quercetin and ADR resulted in potentiation of cytotoxicity, which was measured using a cell counting kit‑8 assay. Flow cytometric analysis revealed that quercetin dose‑dependently promoted cell apoptosis and treatment with a combination of quercetin and ADR caused synergistic enhancement of the apoptotic effect. In addition, treatment of K562/ADR cells with quercetin alone or in combination with ADR resulted in loss of mitochondrial membrane potential, activation of caspase‑8, ‑9 and ‑3, reduced expression of the anti‑apoptotic proteins B‑cell lymphoma (Bcl)‑2 and Bcl‑extra large and enhanced expression of the pro‑apoptotic proteins Bcl‑2‑interacting mediator of cell death, Bcl‑2‑associated death promoter and Bcl‑2‑associated X protein in the cells. Furthermore, the combined treatment of quercetin and ADR synergistically increased the expression of phosphorylated (p‑)c‑Jun N‑terminal kinase and p‑p38 mitogen‑activated protein kinase and decreased the expression of p‑extracellular signal‑regulated kinase in the K562/ADR cells. In addition, the expression of P‑glycoprotein was significantly decreased following treatment with quercetin alone or in combination with ADR. These findings demonstrated that quercetin is important in MDR and may be developed into a new reversal agent for cancer chemotherapy.

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