Docosahexaenoic Acid Induces Cell Death in Human Non-Small Cell Lung Cancer Cells by Repressing mTOR via AMPK Activation and PI3K/Akt Inhibition

BioMed Research International
Nayeong KimKyu Lim

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 NS...Continue Reading

References

Feb 11, 2003·Cell Structure and Function·Noboru MizushimaTamotsu Yoshimori
Aug 18, 2004·Genes & Development·Nissim Hay, Nahum Sonenberg
Jul 20, 2005·The Journal of Biological Chemistry·Annett Hahn-WindgassenNissim Hay
Aug 3, 2006·Nature Reviews. Drug Discovery·Sandrine FaivreEric Raymond
Mar 7, 2007·Current Topics in Developmental Biology·Devrim Gozuacik, Adi Kimchi
Aug 23, 2007·Nature Reviews. Molecular Cell Biology·D Grahame Hardie
Nov 17, 2007·Genes & Development·Noboru Mizushima
Nov 29, 2007·Prostaglandins, Leukotrienes, and Essential Fatty Acids·Jing X Kang
Mar 4, 2008·Methods : a Companion to Methods in Enzymology·Zbigniew DarzynkiewiczHong Zhao
May 16, 2008·The Journal of Nutritional Biochemistry·Joe-Lin du Toit-KohnAnna-Mart Engelbrecht
Aug 6, 2008·Apoptosis : an International Journal on Programmed Cell Death·Simona SeriniGabriella Calviello
Nov 15, 2008·Cell Death and Differentiation·C M Fader, M I Colombo
Jun 3, 2009·Genes & Development·Simon WilkinsonKevin M Ryan
Aug 6, 2009·Annual Review of Genetics·Congcong He, Daniel J Klionsky
Sep 3, 2009·Annals of the New York Academy of Sciences·Sun En LeeHyeyoung Kim
Oct 9, 2009·Journal of Cell Science·Mathieu Laplante, David M Sabatini
Mar 13, 2010·The Journal of Pathology·Danielle GlickKay F Macleod
Apr 7, 2010·Cancer Research and Treatment : Official Journal of Korean Cancer Association·Eunsook Nam, Chaehwa Park
Sep 3, 2010·Nature Cell Biology·Sharon A Tooze, Tamotsu Yoshimori
Oct 19, 2010·Evidence-based Complementary and Alternative Medicine : ECAM·Peng CaoJiege Huo
Feb 18, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Libing SongMengfeng Li
Jan 4, 2012·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Kyoung-Sub SongKyu Lim
Apr 17, 2012·Cell·Mathieu Laplante, David M Sabatini
Oct 25, 2012·Recent Patents on Anti-cancer Drug Discovery·Caroline MorinÉric Rousseau
Jul 11, 2013·Journal of Oncology·Minfei SuSangita Sinha
Jan 9, 2014·CA: a Cancer Journal for Clinicians·Rebecca SiegelAhmedin Jemal
Jun 2, 2014·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Raghav SundarRoss A Soo
Jun 5, 2014·Frontiers in Bioscience (Landmark Edition)·Hong ShengWeixin Cao

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Citations

Jan 29, 2016·Journal of Clinical Medicine·Donatella D'Eliseo, Francesca Velotti
Jan 27, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Yingchun LiangShilin Yang
Sep 15, 2016·International Journal of Molecular Sciences·Jan ŠrámekJan Kovář
Feb 13, 2018·Cancer Chemotherapy and Pharmacology·Liboria SienaElisabetta Pace
Apr 4, 2018·Cancer Biology & Therapy·Xiaohui YangQingyuan Yang
Feb 2, 2018·Scientific Reports·Nathalia PizatoKelly Grace Magalhães
Feb 12, 2019·Cancer Medicine·Jiaqing LiuLi Zhang
Jun 18, 2019·Journal of the Science of Food and Agriculture·Laís Ferraz BritoLucas Miranda Marques
May 13, 2020·Nutrition and Cancer·Owen M VegaSara Huerta-Yepez
Aug 28, 2021·Nutrients·Perrine VermondenYvan Larondelle
Aug 28, 2021·Nutrients·Tamiris Trevisan de BarrosJacqueline Pontes Monteiro

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BETA
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Xenograft

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DP Controller

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