(09-10-15) Role of autophagy in the ù-3 long chain polyunsaturated fatty acid-induced death of lung cancer A549 cells

QINGHUA YAO,1 TING FU,2 LU WANG,2 YUEBIAO LAI,2 YUQI WANG,2 CHAO XU,2 LULU HUANG,2 and YONG GUO3
1Key Lab of Traditional Chinese Medicine Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China
2The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China
3Department of Oncology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China
Correspondence to: Dr Yong Guo, Department of Oncology, The First Affiliated Hospital of Zhejiang Chinese Medical University, 54 Youdian Road, Hangzhou, Zhejiang 310006, P.R. China, E-mail: moc.361@7401gnoyoug
Author information ► Article notes ► Copyright and License information ►
Received 2014 Jun 23; Accepted 2015 Mar 12.
Copyright © 2015, Spandidos Publications
Abstract
The present study identified that ù-3 long chain polyunsaturated fatty acids (ù-3 PUFAs), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) demonstrate anti-proliferative effects in lung cancer A549 cells. MTS and cytotoxicity assays were conducted to confirm that ù-3 PUFAs induced cell death. Autophagy-associated gene and signaling pathways were also detected. Microtubule-associated protein light chain 3 (LC3) expression was found to be increased subsequent to treatment with DHA and EPA, and the expression of LC3-II was particularly increased. mRFP-GFP-LC3 fluorescence staining and p62 expression levels were used to detect autophagic flux. The present results indicate that DHA and EPA block autophagic flux, suggesting autophagosome accumulation. Subsequent to treatment with DHA and EPA, which interfered with autophagosomes, the expression of Beclin 1 was significantly decreased, while the expression of phosphorylated Akt and phosphorylated mammalian target of rapamycin was significantly increased. Therefore, DHA and EPA exert anti-proliferative effects by inhibiting autophagy in A549 cells, which highlights the potential of DHA and EPA for use in the prevention or treatment of lung cancer.

SOURCE: Oncol Lett. 2015 Jun; 9(6): 2736–2742.
Published online 2015 Apr 9. doi:  10.3892/ol.2015.3110
PMCID: PMC4473716

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