Arctigenin shows preferential cytotoxicity to acidity-tolerant prostate carcinoma PC-3 cells through ROS-mediated mitochondrial damage and the inhibition of PI3K/Akt/mTOR pathway
- Authors
- Lee, Yoon-Jin; Oh, Jeong-Eun; Lee, Sang-Han
- Issue Date
- 10-Nov-2018
- Publisher
- Academic Press
- Keywords
- Arctigenin; Prostate cancer; Chemoresistance; Reactive oxygen species; Extracellular acidity
- Citation
- Biochemical and Biophysical Research Communications, v.505, no.4, pp 1244 - 1250
- Pages
- 7
- Journal Title
- Biochemical and Biophysical Research Communications
- Volume
- 505
- Number
- 4
- Start Page
- 1244
- End Page
- 1250
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/5498
- DOI
- 10.1016/j.bbrc.2018.10.045
- ISSN
- 0006-291X
1090-2104
- Abstract
- Extracellular acidity in the tumor microenvironment contributes to chemoresistance of malignant tumors. The objective of this study was to determine anticancer effects of arctigenin, a novel anti-inflammatory lignan extracted from seeds of Arctium lappa, on acidity-tolerant prostate cancer PC-3AcT cells. The PC-3AcT cells manifested increased tolerance to low-pH media with enhanced percent cell viability and increased resistance to docetaxel compared to their parental PC-3 cells. Arctigenin alone or in combination with docetaxel induced potent cytotoxicity. Preferential sensitization of PC-3AcT cells to arctigenin was accompanied by increased cell fractions with sub-G(0)/G(1) peak and annexin V-PE(+), increased ROS levels, decreased mitochondrial membrane potential and cellular ATP content, and inhibition of PI3K/Akt/mTOR pathway. A series of changes caused by arctigenin were efficiently reversed through reducing ROS levels by radical scavenger N-acetylcysteine, thus placing ROS upstream of arctigenin-driven cytotoxicity. Collectively, these results demonstrate that arctigenin can increase oxidative stress-mediated mitochondrial damage of acidity-tolerant PC-3AcT cells, suggesting that arctigenin might be a potential therapeutic candidate to overcome acidic-microenvironment-associated chemotherapeutic resistance in prostate cancer. (C) 2018 Elsevier Inc. All rights reserved.
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