Effects of P-Glycoprotein and Its Inhibitors on Apoptosis in K562 Cells
| العنوان: | Effects of P-Glycoprotein and Its Inhibitors on Apoptosis in K562 Cells |
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| المؤلفون: | Songshan Tang, Yaqiong Zu, Jun Ma, Zhiyong Yang, Ying Han |
| المصدر: | Molecules, Vol 19, Iss 9, Pp 13061-13075 (2014) Molecules Molecules; Volume 19; Issue 9; Pages: 13061-13075 |
| بيانات النشر: | MDPI AG, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | verapamil, Cell cycle checkpoint, Cell, Pharmaceutical Science, Antineoplastic Agents, Cyclosporins, H108, Caspase 3, PSC833, P-glycoprotein, apoptosis, K562 cells, P-glycoprotein inhibitors, caspase 3, Article, Analytical Chemistry, lcsh:QD241-441, lcsh:Organic chemistry, Drug Discovery, medicine, Humans, ATP Binding Cassette Transporter, Subfamily B, Member 1, Physical and Theoretical Chemistry, Cytotoxicity, Caspase, biology, Organic Chemistry, Cell Cycle Checkpoints, Cell cycle, Flow Cytometry, Molecular biology, Drug Resistance, Multiple, medicine.anatomical_structure, Doxorubicin, Drug Resistance, Neoplasm, Chemistry (miscellaneous), Apoptosis, biology.protein, Molecular Medicine |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| ردمك: | 978-1-306-11307-6 1-306-11307-5 |
| تدمد: | 1420-3049 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::08df7b61a9fc6c644004dd70773c1775 https://doi.org/10.3390/molecules190913061 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....08df7b61a9fc6c644004dd70773c1775 |
| قاعدة البيانات: | OpenAIRE |
| ردمك: | 9781306113076 1306113075 |
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| تدمد: | 14203049 |