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Molecules 2014, 19(9), 13061-13075;

Effects of P-Glycoprotein and Its Inhibitors on Apoptosis in K562 Cells

Department of Health Statistics, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, China
HUYA Bioscience International LLC, 3 Haidian Avenue, Haidian District, Beijing 100080, China
Department of Biochemistry and Molecular Biology, School of Basic Courses, Guangdong Pharmaceutical University, 280 Waihuandong Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, China
Biotherapy Center of Tianjin Cancer Institute and Hospital, Tianjin Medical University, Tiyuanbei, Huanhuxi Road, Hexi District, Tianjin 300060, China
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Received: 5 June 2014 / Revised: 12 August 2014 / Accepted: 18 August 2014 / Published: 25 August 2014
(This article belongs to the Section Medicinal Chemistry)
Full-Text   |   PDF [915 KB, uploaded 25 August 2014]   |  


P-glycoprotein (P-gp) is a major factor in multidrug resistance (MDR) which is a serious obstacle in chemotherapy. P-gp has also been implicated in causing apoptosis of tumor cells, which was shown to be another important mechanism of MDR recently. To study the influence of P-gp in tumor cell apoptosis, K562/A cells (P-gp+) and K562/S cells (P-gp−) were subjected to doxorubicin (Dox), serum withdrawal, or independent co-incubation with multiple P-gp inhibitors, including valspodar (PSC833), verapamil (Ver) and H108 to induce apoptosis. Apoptosis was simultaneously detected by apoptotic rate, cell cycle by flow cytometry and cysteine aspartic acid-specific protease 3 (caspase 3) activity by immunoassay. Cytotoxicity and apoptosis induced by PSC833 were evaluated through an MTT method and apoptosis rate, and cell cycle combined with caspase 3 activity, respectively. The results show that K562/A cells are more resistant to apoptosis and cell cycle arrest than K562/S cells after treatment with Dox or serum deprivation. The apoptosis of K562/A cells increased after co-incubation with each of the inhibitors of P-gp. P-gp inhibitors also enhanced cell cycle arrest in K562/A cell. PSC833 most strikingly decreased viability and led to apoptosis and S phase arrest of cell cycle in K562/A cells. Our study demonstrates that P-gp inhibits the apoptosis of tumor cells in addition to participating in the efflux of intracellular chemotherapy drugs. The results of the caspase 3 activity assay also suggest that the role of P-gp in apoptosis avoidance is caspase-related. View Full-Text
Keywords: P-glycoprotein; apoptosis; K562 cells; P-glycoprotein inhibitors; caspase 3; PSC833; verapamil; H108 P-glycoprotein; apoptosis; K562 cells; P-glycoprotein inhibitors; caspase 3; PSC833; verapamil; H108

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Zu, Y.; Yang, Z.; Tang, S.; Han, Y.; Ma, J. Effects of P-Glycoprotein and Its Inhibitors on Apoptosis in K562 Cells. Molecules 2014, 19, 13061-13075.

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