Academic Journal
Acquired drug resistance interferes with the susceptibility of prostate cancer cells to metabolic stress
| العنوان: | Acquired drug resistance interferes with the susceptibility of prostate cancer cells to metabolic stress |
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| المؤلفون: | Jessica Catapano, Marcin Luty, Tomasz Wróbel, Maciej Pudełek, Katarzyna Piwowarczyk, Sylwia Kędracka-Krok, Maciej Siedlar, Zbigniew Madeja, Jarosław Czyż |
| المصدر: | Cellular & Molecular Biology Letters, Vol 27, Iss 1, Pp 1-19 (2022) |
| بيانات النشر: | BMC |
| سنة النشر: | 2022 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | Metabolic stress, Drug resistance, Prostate cancer, Metabolic adaptation, Metformin, Cytology, QH573-671 |
| الوصف: | Background Metformin is an inhibitor of oxidative phosphorylation that displays an array of anticancer activities. The interference of metformin with the activity of multi-drug resistance systems in cancer cells has been reported. However, the consequences of the acquired chemoresistance for the adaptative responses of cancer cells to metformin-induced stress and for their phenotypic evolution remain unaddressed. Methods Using a range of phenotypic and metabolic assays, we assessed the sensitivity of human prostate cancer PC-3 and DU145 cells, and their drug-resistant lineages (PC-3_DCX20 and DU145_DCX20), to combined docetaxel/metformin stress. Their adaptation responses have been assessed, in particular the shifts in their metabolic profile and invasiveness. Results Metformin increased the sensitivity of PC-3 wild-type (WT) cells to docetaxel, as illustrated by the attenuation of their motility, proliferation, and viability after the combined drug application. These effects correlated with the accumulation of energy carriers (NAD(P)H and ATP) and with the inactivation of ABC drug transporters in docetaxel/metformin-treated PC-3 WT cells. Both PC-3 WT and PC-3_DCX20 reacted to metformin with the Warburg effect; however, PC-3_DCX20 cells were considerably less susceptible to the cytostatic/misbalancing effects of metformin. Concomitantly, an epithelial–mesenchymal transition and Cx43 upregulation was seen in these cells, but not in other more docetaxel/metformin-sensitive DU145_DCX20 populations. Stronger cytostatic effects of the combined fenofibrate/docetaxel treatment confirmed that the fine-tuning of the balance between energy supply and expenditure determines cellular welfare under metabolic stress. Conclusions Collectively, our data identify the mechanisms that underlie the limited potential of metformin for the chemotherapy of drug-resistant tumors. Metformin can enhance the sensitivity of cancer cells to chemotherapy by inducing their metabolic decoupling/imbalance. However, the acquired ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1425-8153 1689-1392 |
| Relation: | https://doi.org/10.1186/s11658-022-00400-1; https://doaj.org/toc/1425-8153; https://doaj.org/toc/1689-1392; https://doaj.org/article/10d26827c51d47bcb480ad68f24bfa43 |
| DOI: | 10.1186/s11658-022-00400-1 |
| الاتاحة: | https://doi.org/10.1186/s11658-022-00400-1 https://doaj.org/article/10d26827c51d47bcb480ad68f24bfa43 |
| رقم الانضمام: | edsbas.B4D2BDCB |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 14258153 16891392 |
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| DOI: | 10.1186/s11658-022-00400-1 |