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.
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.
['Lahmar|Aida|A|', 'Mathey|Aline|A|', 'Aires|Virginie|V|', 'Elgueder|Dorra|D|', 'Vejux|Anne|A|0000-0002-4063-9680', 'Khlifi|Rihab|R|', 'Sioud|Fairouz|F|', 'Chekir-Ghedira|Leila|L|', 'Delmas|Dominique|D|']
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 D017209:Apoptosis D002453:Cell Cycle D016923:Cell Death D045744:Cell Line, Tumor D002470:Cell Survival D004317:Doxorubicin D018432:Drug Resistance, Multiple D019008:Drug Resistance, Neoplasm D005260:Female D006801:Humans D019684:Magnoliopsida D009822:Oils, Volatile D010936:Plant Extracts D010938:Plant Oils D017382:Reactive Oxygen Species D012509:Sarcoma D012983:Soft Tissue Neoplasms D031367:Teucrium D014594:Uterine Neoplasms
essential oils chemosensitization uterine sarcoma doxorubicin P-glycoprotein