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

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 apopto...

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Autores principales: Zu, Yaqiong, Yang, Zhiyong, Tang, Songshan, Han, Ying, Ma, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6270982/
https://www.ncbi.nlm.nih.gov/pubmed/25157469
http://dx.doi.org/10.3390/molecules190913061
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author Zu, Yaqiong
Yang, Zhiyong
Tang, Songshan
Han, Ying
Ma, Jun
author_facet Zu, Yaqiong
Yang, Zhiyong
Tang, Songshan
Han, Ying
Ma, Jun
author_sort Zu, Yaqiong
collection PubMed
description 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.
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spelling pubmed-62709822018-12-27 Effects of P-Glycoprotein and Its Inhibitors on Apoptosis in K562 Cells Zu, Yaqiong Yang, Zhiyong Tang, Songshan Han, Ying Ma, Jun Molecules Article 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. MDPI 2014-08-25 /pmc/articles/PMC6270982/ /pubmed/25157469 http://dx.doi.org/10.3390/molecules190913061 Text en © 2014 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Zu, Yaqiong
Yang, Zhiyong
Tang, Songshan
Han, Ying
Ma, Jun
Effects of P-Glycoprotein and Its Inhibitors on Apoptosis in K562 Cells
title Effects of P-Glycoprotein and Its Inhibitors on Apoptosis in K562 Cells
title_full Effects of P-Glycoprotein and Its Inhibitors on Apoptosis in K562 Cells
title_fullStr Effects of P-Glycoprotein and Its Inhibitors on Apoptosis in K562 Cells
title_full_unstemmed Effects of P-Glycoprotein and Its Inhibitors on Apoptosis in K562 Cells
title_short Effects of P-Glycoprotein and Its Inhibitors on Apoptosis in K562 Cells
title_sort effects of p-glycoprotein and its inhibitors on apoptosis in k562 cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6270982/
https://www.ncbi.nlm.nih.gov/pubmed/25157469
http://dx.doi.org/10.3390/molecules190913061
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