Reduced intracellular drug accumulation in drug-resistant leukemia cells is not solely due to MDR-mediated efflux but also to decreased uptake
Expression of ABC family transporter proteins that promote drug efflux from cancer cells is a widely observed mechanism of multi-drug resistance of cancer cells. Cell adaptation in long-term culture of HL60 leukemic cells in the presence of chemotherapy leads to induction and maintenance of the ABC...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-10-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fonc.2014.00306/full |
| _version_ | 1828963837026500608 |
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| author | Angela Oliveira Pisco Angela Oliveira Pisco Dean Andrew Jackson Sui eHuang Sui eHuang |
| author_facet | Angela Oliveira Pisco Angela Oliveira Pisco Dean Andrew Jackson Sui eHuang Sui eHuang |
| author_sort | Angela Oliveira Pisco |
| collection | DOAJ |
| description | Expression of ABC family transporter proteins that promote drug efflux from cancer cells is a widely observed mechanism of multi-drug resistance of cancer cells. Cell adaptation in long-term culture of HL60 leukemic cells in the presence of chemotherapy leads to induction and maintenance of the ABC transporters expression, preventing further accumulation of drugs. However, we found that decreased accumulation of drugs and fluorescent dyes was also contributed by a reduced uptake by the resistant cells. Confocal time-lapse microscopy and flow cytometry revealed that fluid-phase endocytosis was diminished in drug-resistant cells compared to drug-sensitive cells. Drug uptake was increased by insulin co-treatment when cells were grown in methylcellulose and monitored under the microscope, but not when cultured in suspension. We propose that multi-drug resistance is not solely achieved by enhanced efflux capacity but also by supressed intake of the drug offering an alternative target to overcome drug resistance or potentiate chemotherapy. |
| first_indexed | 2024-12-14T10:36:45Z |
| format | Article |
| id | doaj.art-e3008cb0937a43049b46eef53a325d2f |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-14T10:36:45Z |
| publishDate | 2014-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-e3008cb0937a43049b46eef53a325d2f2022-12-21T23:05:53ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2014-10-01410.3389/fonc.2014.00306110738Reduced intracellular drug accumulation in drug-resistant leukemia cells is not solely due to MDR-mediated efflux but also to decreased uptakeAngela Oliveira Pisco0Angela Oliveira Pisco1Dean Andrew Jackson2Sui eHuang3Sui eHuang4The University of ManchesterInstitute for Systems BiologyThe University of ManchesterInstitute for Systems BiologyUniversity of CalgaryExpression of ABC family transporter proteins that promote drug efflux from cancer cells is a widely observed mechanism of multi-drug resistance of cancer cells. Cell adaptation in long-term culture of HL60 leukemic cells in the presence of chemotherapy leads to induction and maintenance of the ABC transporters expression, preventing further accumulation of drugs. However, we found that decreased accumulation of drugs and fluorescent dyes was also contributed by a reduced uptake by the resistant cells. Confocal time-lapse microscopy and flow cytometry revealed that fluid-phase endocytosis was diminished in drug-resistant cells compared to drug-sensitive cells. Drug uptake was increased by insulin co-treatment when cells were grown in methylcellulose and monitored under the microscope, but not when cultured in suspension. We propose that multi-drug resistance is not solely achieved by enhanced efflux capacity but also by supressed intake of the drug offering an alternative target to overcome drug resistance or potentiate chemotherapy.http://journal.frontiersin.org/Journal/10.3389/fonc.2014.00306/fullEndocytosis-related multidrug resistanceABC transporters dependent drug resistanceCellular responses to anticancer drugsNovel mechanism of multidrug resistanceAcute Myeloid Leukemia model |
| spellingShingle | Angela Oliveira Pisco Angela Oliveira Pisco Dean Andrew Jackson Sui eHuang Sui eHuang Reduced intracellular drug accumulation in drug-resistant leukemia cells is not solely due to MDR-mediated efflux but also to decreased uptake Frontiers in Oncology Endocytosis-related multidrug resistance ABC transporters dependent drug resistance Cellular responses to anticancer drugs Novel mechanism of multidrug resistance Acute Myeloid Leukemia model |
| title | Reduced intracellular drug accumulation in drug-resistant leukemia cells is not solely due to MDR-mediated efflux but also to decreased uptake |
| title_full | Reduced intracellular drug accumulation in drug-resistant leukemia cells is not solely due to MDR-mediated efflux but also to decreased uptake |
| title_fullStr | Reduced intracellular drug accumulation in drug-resistant leukemia cells is not solely due to MDR-mediated efflux but also to decreased uptake |
| title_full_unstemmed | Reduced intracellular drug accumulation in drug-resistant leukemia cells is not solely due to MDR-mediated efflux but also to decreased uptake |
| title_short | Reduced intracellular drug accumulation in drug-resistant leukemia cells is not solely due to MDR-mediated efflux but also to decreased uptake |
| title_sort | reduced intracellular drug accumulation in drug resistant leukemia cells is not solely due to mdr mediated efflux but also to decreased uptake |
| topic | Endocytosis-related multidrug resistance ABC transporters dependent drug resistance Cellular responses to anticancer drugs Novel mechanism of multidrug resistance Acute Myeloid Leukemia model |
| url | http://journal.frontiersin.org/Journal/10.3389/fonc.2014.00306/full |
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