Drug Efflux Transporters Are Overexpressed in Short-Term Tamoxifen-Induced MCF7 Breast Cancer Cells
Tamoxifen is the first line drug used in the treatment of estrogen receptor-positive (ER+) breast cancer. The development of multidrug resistance (MDR) to tamoxifen remains a major challenge in the treatment of cancer. One of the mechanisms related to MDR is decrease of drug influx via overexpressio...
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doaj-cb53c1d8cb7a482ca18583fceaf5394d2020-11-25T03:17:05ZengHindawi LimitedAdvances in Pharmacological Sciences1687-63341687-63422016-01-01201610.1155/2016/67024246702424Drug Efflux Transporters Are Overexpressed in Short-Term Tamoxifen-Induced MCF7 Breast Cancer CellsDesak Gede Budi Krisnamurti0Melva Louisa1Erlia Anggraeni2Septelia Inawati Wanandi3Department of Medical Pharmacy, Faculty of Medicine, University of Indonesia, Jakarta 10430, IndonesiaDepartment of Pharmacology and Therapeutics, Faculty of Medicine, University of Indonesia, Jakarta 10430, IndonesiaMaster Program in Biomedicine, Faculty of Medicine, University of Indonesia, Jakarta 10430, IndonesiaDepartment of Biochemistry and Molecular Biology, Faculty of Medicine, University of Indonesia, Jakarta 10430, IndonesiaTamoxifen is the first line drug used in the treatment of estrogen receptor-positive (ER+) breast cancer. The development of multidrug resistance (MDR) to tamoxifen remains a major challenge in the treatment of cancer. One of the mechanisms related to MDR is decrease of drug influx via overexpression of drug efflux transporters such as P-glycoprotein (P-gp/MDR1), multidrug resistance associated protein (MRP), or BCRP (breast cancer resistance protein). We aimed to investigate whether the sensitivity of tamoxifen to the cells is maintained through the short period and whether the expressions of several drug efflux transporters have been upregulated. We exposed MCF7 breast cancer cells with tamoxifen 1 μM for 10 passages (MCF7 (T)). The result showed that MCF7 began to lose their sensitivity to tamoxifen from the second passage. MCF7 (T) also showed a significant increase in all transporters examined compared with MCF7 parent cells. The result also showed a significant increase of CC50 in MCF7 (T) compared to that in MCF7 (97.54 μM and 3.04 μM, resp.). In conclusion, we suggest that the expression of several drug efflux transporters such as P-glycoprotein, MRP2, and BCRP might be used and further studied as a marker in the development of tamoxifen resistance.http://dx.doi.org/10.1155/2016/6702424 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Desak Gede Budi Krisnamurti Melva Louisa Erlia Anggraeni Septelia Inawati Wanandi |
spellingShingle |
Desak Gede Budi Krisnamurti Melva Louisa Erlia Anggraeni Septelia Inawati Wanandi Drug Efflux Transporters Are Overexpressed in Short-Term Tamoxifen-Induced MCF7 Breast Cancer Cells Advances in Pharmacological Sciences |
author_facet |
Desak Gede Budi Krisnamurti Melva Louisa Erlia Anggraeni Septelia Inawati Wanandi |
author_sort |
Desak Gede Budi Krisnamurti |
title |
Drug Efflux Transporters Are Overexpressed in Short-Term Tamoxifen-Induced MCF7 Breast Cancer Cells |
title_short |
Drug Efflux Transporters Are Overexpressed in Short-Term Tamoxifen-Induced MCF7 Breast Cancer Cells |
title_full |
Drug Efflux Transporters Are Overexpressed in Short-Term Tamoxifen-Induced MCF7 Breast Cancer Cells |
title_fullStr |
Drug Efflux Transporters Are Overexpressed in Short-Term Tamoxifen-Induced MCF7 Breast Cancer Cells |
title_full_unstemmed |
Drug Efflux Transporters Are Overexpressed in Short-Term Tamoxifen-Induced MCF7 Breast Cancer Cells |
title_sort |
drug efflux transporters are overexpressed in short-term tamoxifen-induced mcf7 breast cancer cells |
publisher |
Hindawi Limited |
series |
Advances in Pharmacological Sciences |
issn |
1687-6334 1687-6342 |
publishDate |
2016-01-01 |
description |
Tamoxifen is the first line drug used in the treatment of estrogen receptor-positive (ER+) breast cancer. The development of multidrug resistance (MDR) to tamoxifen remains a major challenge in the treatment of cancer. One of the mechanisms related to MDR is decrease of drug influx via overexpression of drug efflux transporters such as P-glycoprotein (P-gp/MDR1), multidrug resistance associated protein (MRP), or BCRP (breast cancer resistance protein). We aimed to investigate whether the sensitivity of tamoxifen to the cells is maintained through the short period and whether the expressions of several drug efflux transporters have been upregulated. We exposed MCF7 breast cancer cells with tamoxifen 1 μM for 10 passages (MCF7 (T)). The result showed that MCF7 began to lose their sensitivity to tamoxifen from the second passage. MCF7 (T) also showed a significant increase in all transporters examined compared with MCF7 parent cells. The result also showed a significant increase of CC50 in MCF7 (T) compared to that in MCF7 (97.54 μM and 3.04 μM, resp.). In conclusion, we suggest that the expression of several drug efflux transporters such as P-glycoprotein, MRP2, and BCRP might be used and further studied as a marker in the development of tamoxifen resistance. |
url |
http://dx.doi.org/10.1155/2016/6702424 |
work_keys_str_mv |
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