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

Journal Article · Thu Nov 15 04:00:00 EST 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.10.045· OSTI ID:23134098

Lee, Yoon-Jin; Oh, Jeong-Eun; Lee, Sang-Han ^[1]

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1. Department of Biochemistry, College of Medicine, Soonchunhyang University, Cheonan, 31151 (Korea, Republic of)

Highlights: • Arctigenin induces preferential cytotoxicity to acid-tolerant PC-3AcT cells. • Arctigenin induced cytotoxicity is linked to ROS-mediated mitochondrial damage. • Arctigenin-induced ROS accumulation was associated with ATP depletion. • PI3K/Akt/mTOR pathway is one of the targets of arctigenin-induced oxidative insults. 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{sub 0}/G{sub 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.

• OSTI ID: 23134098
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 505; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CARCINOMAS
INFLAMMATION
MITOCHONDRIA
PROSTATE