期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 505, 期 4, 页码 1244-1250出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2018.10.045
关键词
Arctigenin; Prostate cancer; Chemoresistance; Reactive oxygen species; Extracellular acidity
资金
- Basic Science Research Program through the National Research Foundation (NRF) of Korea - Ministry of Education [NRF-2017R1D1A3B04031891]
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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