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Overcoming Multidrug Resistance by Activating Unfolded Protein Response of the Endoplasmic Reticulum in Cisplatin-Resistant A2780/CisR Ovarian Cancer Cells

BMB Reports 2020년 53권 2호 p.88 ~ 93
정의택 ( Jung Eui-Taek ) - Konkuk University Sanghuh College of Life Sciences Department of Biological Sciences

고동수 ( Koh Dong-Soo ) - Dongduk Women’s University Department of Applied Chemistry
임융호 ( Lim Yoong-Ho ) - Konkuk University Division of Bioscience and Biotechnology
신순영 ( Shin Soon-Young ) - Konkuk University Sanghuh College of Life Sciences Department of Biological Sciences
이영한 ( Lee Young-Han ) - Konkuk University Sanghuh College of Life Sciences Department of Biological Sciences

Abstract


Cisplatin is a widely used anti-cancer agent. However, the effectiveness of cisplatin has been limited by the commonly developed drug resistance. This study aimed to investigate the potential effects of endoplasmic reticulum (ER) stress to overcome drug resistance using the cisplatin-resistant A2780/CisR ovarian cancer cell model. The synthetic chalcone derivative (E)-3-(3,5-dimethoxyphenyl)-1-(2-methoxyphenyl)prop-2-en-1-one (named DPP23) is an ER stress inducer. We found that DPP23 triggered apoptosis in both parental cisplatinsensitive A2780 and cisplatin-resistant A2780/CisR ovarian cancer cells due to activation of reactive oxygen species (ROS)-mediated unfolded protein response (UPR) pathway in the endoplasmic reticulum. This result suggests that ROSmediated UPR activation is potential in overcoming drug resistance. DPP23 can be used as a target pharmacophore for the development of novel chemotherapeutic agents capable of overcoming drug resistance in cancer cells, particularly ovarian cancer cells.

키워드

Cisplatin resistance; DPP23; Ovarian cancer; Reactive oxygen species; Unfolded protein response
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