Abstract | BACKGROUND:
Multidrug resistance proteins are one of the most important factors that cause chemotherapy resistance, which in turn reduces therapeutic efficacy and survival for cancer patients. Tunicamycin is one of the most well-known inhibitors of N-glycosylation and is considered a powerful adjunct that can increase the effectiveness of many drugs. Tunicamycin blocks the first step of P-gp ( glycoprotein P) and BCRP ( breast cancer resistance protein) N-glycosylation, which is a very important modification for the activity and cellular localisation of these proteins. METHODS: RESULTS: In this study, we showed via the MTT assay that tunicamycin significantly decreased the viability of cancer cell lines that were co-treated with a chemotherapeutic drug. Western blot analysis showed that, in LoVo/Dx and W1PR cells, tunicamycin treatment resulted in the expression of a 70kDa P-gp protein instead of the mature 170kDa P-gp. Treatment with MG132 or BMA fully suppressed the effect of tunicamycin in the case of W1PR cells only. In tunicamycin-treated W1TR cells, the size of the BCRP protein did not differ from that of its native unglycosylated form. In tunicamycin-treated A2780T1 cells, BCRP expression was completely inhibited, but pre-treatment with MG132 or BMA suppressed the effect of tunicamycin. Immunocytochemistry analysis indicated that tunicamycin only affected the translocation of P-gp but not that of BCRP. After treatment, we observed higher P-gp expression in the cytoplasm than at the cell membrane. CONCLUSIONS: Our results indicated that tunicamycin may enhance the effect of chemotherapy by interfering with the localisation and function of transporter proteins that are responsible for multidrug resistance.
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Authors | Karolina Wojtowicz, Radosław Januchowski, Michał Nowicki, Maciej Zabel |
Journal | Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
(Biomed Pharmacother)
Vol. 74
Pg. 49-56
(Aug 2015)
ISSN: 1950-6007 [Electronic] France |
PMID | 26349962
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 Elsevier Masson SAS. All rights reserved. |
Chemical References |
- ATP Binding Cassette Transporter, Subfamily B
- ATP Binding Cassette Transporter, Subfamily B, Member 1
- Antineoplastic Agents
- Tunicamycin
- Topotecan
- Doxorubicin
- Paclitaxel
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Topics |
- ATP Binding Cassette Transporter, Subfamily B
(metabolism)
- ATP Binding Cassette Transporter, Subfamily B, Member 1
(metabolism)
- Antineoplastic Agents
(pharmacology)
- Cell Line, Tumor
- Colorectal Neoplasms
(drug therapy, pathology)
- Doxorubicin
(pharmacology)
- Drug Resistance, Multiple
- Drug Resistance, Neoplasm
- Female
- Glycosylation
(drug effects)
- Humans
- Ovarian Neoplasms
(drug therapy, pathology)
- Paclitaxel
(pharmacology)
- Phenotype
- Topotecan
(pharmacology)
- Tunicamycin
(pharmacology)
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