Essential Oils, Pituranthos chloranthus and Teucrium ramosissimum, Chemosensitize Resistant Human Uterine Sarcoma MES-SA/Dx5 Cells to Doxorubicin by Inducing Apoptosis and Targeting P-Glycoprotein
| Autor: | Virginie Aires, Rihab Khlifi, Dominique Delmas, Anne Vejux, Aline Mathey, Aida Lahmar, Fairouz Sioud, Dorra Elgueder, Leila Chekir-Ghedira |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Programmed cell death uterine sarcoma P-glycoprotein doxorubicin 03 medical and health sciences 0302 clinical medicine medicine Doxorubicin TX341-641 Viability assay essential oils Nutrition and Dietetics biology Chemistry Nutrition. Foods and food supply Cell cycle chemosensitization 030104 developmental biology Apoptosis Cell culture 030220 oncology & carcinogenesis Cancer research biology.protein Intracellular Food Science medicine.drug |
| Zdroj: | Nutrients, Vol 13, Iss 1719, p 1719 (2021) Nutrients Volume 13 Issue 5 |
| ISSN: | 2072-6643 |
| Popis: | The multidrug resistance phenotype is a global phenomenon and causes chemotherapy failure in various cancers, such as in uterine sarcomas that have a high mortality rate. To overcome this phenotype, there is growing research interest in developing new treatment strategies. In this study, we highlight the potential of two essential oils from the Apiaceae family, Pituranthos chloranthus (PC) and Teucrium ramosissimum Desf. (TR), to act as chemopreventive and chemosensitizing agents against two uterine sarcoma cell lines, MES-SA and P-gp-overexpressing MES-SA/Dx5 cells. We found that PC and TR were able to inhibit the cell viability of sensitive MES-SA and resistant MES-SA/Dx5 cells by a slight modulation of the cell cycle and its regulators, but also through a significant induction of apoptosis. The molecular mechanism involved both caspase pathways associated with an overproduction of reactive oxygen species (ROS) and mitochondrial membrane depolarization. Very interestingly, the combination of doxorubicin with PC or TR induced a synergism to increase cell death in resistant MES-SA/Dx5 cells and, subsequently, had the benefit of decreasing the resistance index to doxorubicin. These synergistic effects were reinforced by a decrease in P-gp expression and its P-gp adenosine triphosphatase (ATPase) activity, which subsequently led to intracellular doxorubicin accumulation in resistant sarcoma cells. |
| Databáze: | OpenAIRE |
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