Effects of P-Glycoprotein and Its Inhibitors on Apoptosis in K562 Cells
AbstractP-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
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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.
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(9):13061-13075.Chicago/Turabian Style
Zu, Yaqiong; Yang, Zhiyong; Tang, Songshan; Han, Ying; Ma, Jun. 2014. "Effects of P-Glycoprotein and Its Inhibitors on Apoptosis in K562 Cells." Molecules 19, no. 9: 13061-13075.