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Overcoming multidrug resistance by activating unfolded protein response of the endoplasmic reticulum in cisplatin-resistant A2780/CisR ovarian cancer cells

  • Jung, Euitaek (Department of Biological Sciences, Sanghuh College of Life Sciences, Konkuk University) ;
  • Koh, Dongsoo (Department of Applied Chemistry, Dongduk Women's University) ;
  • Lim, Yoongho (Division of Bioscience and Biotechnology, BMIC, Konkuk University) ;
  • Shin, Soon Young (Department of Biological Sciences, Sanghuh College of Life Sciences, Konkuk University) ;
  • Lee, Young Han (Department of Biological Sciences, Sanghuh College of Life Sciences, Konkuk University)
  • Received : 2019.04.15
  • Accepted : 2019.06.03
  • Published : 2020.02.29

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 cisplatin-sensitive 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 ROS-mediated 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.

Keywords

References

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