학술논문
Docosahexaenoic Acid Induces Cell Death in Human Non-Small Cell Lung Cancer Cells by Repressing mTOR via AMPK Activation and PI3K/Akt Inhibition.
Document Type
Article
Author
Source
Subject
*AUTOPHAGY
*ANIMAL experimentation
*APOPTOSIS
*BIOLOGICAL models
*BIOPHYSICS
*CELL death
*CELL lines
*CELLULAR signal transduction
*DOSE-effect relationship in pharmacology
*FLOW cytometry
*FLUORESCENT antibody technique
*IMMUNOHISTOCHEMISTRY
*LUNG cancer
*RESEARCH methodology
*MICE
*MICROSCOPY
*PHOSPHOTRANSFERASES
*POLYMERASE chain reaction
*PROBABILITY theory
*PROTEIN kinases
*RESEARCH funding
*SPECTROPHOTOMETRY
*T-test (Statistics)
*WESTERN immunoblotting
*XENOGRAFTS
*DOCOSAHEXAENOIC acid
*DESCRIPTIVE statistics
*IN vitro studies
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
Language
ISSN
2314-6133
Abstract
The anticancer properties and mechanism of action of omega-3 polyunsaturated fatty acids (ω3-PUFAs) have been demonstrated in several cancers; however, the mechanism in lung cancer remains unclear. Here, we show that docosahexaenoic acid (DHA), a ω3-PUFA, induced apoptosis and autophagy in non-small cell lung cancer (NSCLC) cells. DHA-induced cell death was accompanied by AMP-activated protein kinase (AMPK) activation and inactivated phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling. Knocking down AMPK and overexpressing Akt increased mTOR activity and attenuated DHA-induced cell death, suggesting that DHA induces cell death via AMPK- and Akt-regulated mTOR inactivation. This was confirmed in Fat-1 transgenic mice, which produce ω3-PUFAs. Lewis lung cancer (LLC) tumor cells implanted into Fat-1 mice showed slower growth, lower phospho-Akt levels, and higher levels of apoptosis and autophagy than cells implanted into wild-type mice. Taken together, these data suggest that DHA-induced apoptosis and autophagy in NSCLC cells are associated with AMPK activation and PI3K/Akt inhibition, which in turn lead to suppression of mTOR; thus ω3-PUFAs may be utilized as potential therapeutic agents for NSCLC treatment. [ABSTRACT FROM AUTHOR]