Inhibition of autophagy sensitizes lignan-induced endoplasmic reticulum stress-mediated cell death
  • Kwon, Junhee
  • Lee, Yunkyeong
  • Jeong, Ji Hye
  • Ryu, Jae-Ha
  • Kim, Keun Il
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초록

Relationship between autophagy and endoplasmic reticulum (ER) stress and their application to treat cancer have been actively studied these days. Recently, a lignan [(-)-(2R, 3R)-1,4-O-diferuloylsecoisolariciresinol, DFS] from Alnus japonica has been found to reduce the viability of colon cancer cells. In this study, we have observed DFS-induced autophagy in a variety of cancer cell lines. In addition, DFS led to ER stress, based on the activation of unfolded protein response (UPR) transducers and an elevated expression of UPR target genes in prostate and colon cancer cells. Further investigation has shown that DFS triggered the activation of AMP-activated protein kinase (AMPK) signaling and nuclear translocation of transcription factor EB (TFEB). Furthermore, the cytotoxicity of DFS was potentiated by the co-treatment of autophagy inhibitor in these cancer cells. This study has provided a noble implication that the combination of DFS and autophagy inhibition exerts a synergistic effect in cancer treatment. (C) 2020 Elsevier Inc. All rights reserved.

키워드

DFSAutophagyER stressAMPK signalingTFEBCell deathER STRESSAMPKCOMPONENTSACTIVATIONPROTEINTFEB
제목
Inhibition of autophagy sensitizes lignan-induced endoplasmic reticulum stress-mediated cell death
저자
Kwon, JunheeLee, YunkyeongJeong, Ji HyeRyu, Jae-HaKim, Keun Il
DOI
10.1016/j.bbrc.2020.03.081
발행일
2020-05
유형
Article
저널명
Biochemical and Biophysical Research Communications
526
2
페이지
300 ~ 305