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精油通过诱导细胞凋亡和靶向 P-糖蛋白使多柔比星耐药的人子宫肉瘤 MES-SA/Dx5 细胞对多柔比星增敏。

Essential Oils, and , Chemosensitize Resistant Human Uterine Sarcoma MES-SA/Dx5 Cells to Doxorubicin by Inducing Apoptosis and Targeting P-Glycoprotein.

机构信息

Research Unit Bioactive Natural Products and Biotechnology UR17ES49, Faculty of Dental Medicine of Monastir, University of Monastir, Avicenne Street, Monastir 5000, Tunisia.

Université de Bourgogne Franche-Comté, F-21000 Dijon, France.

出版信息

Nutrients. 2021 May 19;13(5):1719. doi: 10.3390/nu13051719.

DOI:10.3390/nu13051719
PMID:34069490
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8160977/
Abstract

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, (PC) and 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.

摘要

多药耐药表型是一种全球性现象，导致各种癌症的化疗失败，例如子宫肉瘤，其死亡率很高。为了克服这种表型，人们越来越关注开发新的治疗策略。在这项研究中，我们强调了来自伞形科的两种精油，（PC）和 （TR），作为化学预防和化学增敏剂对抗两种子宫肉瘤细胞系，MES-SA 和 P-糖蛋白过表达的 MES-SA/Dx5 细胞的潜力。我们发现 PC 和 TR 能够通过轻微调节细胞周期及其调节剂来抑制敏感的 MES-SA 和耐药的 MES-SA/Dx5 细胞的活力，并且还通过显著诱导细胞凋亡来抑制细胞活力。所涉及的分子机制包括与活性氧 (ROS) 过度产生和线粒体膜去极化相关的两种半胱天冬酶途径。非常有趣的是，阿霉素与 PC 或 TR 的联合使用诱导协同作用，增加耐药 MES-SA/Dx5 细胞的细胞死亡，随后降低阿霉素的耐药指数。这些协同作用通过降低 P-糖蛋白表达及其 P-糖蛋白三磷酸腺苷酶 (ATPase) 活性得到加强，随后导致耐药肉瘤细胞内阿霉素的积累。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c7a/8160977/fe9411455a7d/nutrients-13-01719-g011.jpg
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