Abstract. The present study identified that ω-3 long chain polyunsaturated fatty acids (ω-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 ω-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. IntroductionLung cancer is the leading cause of cancer-associated mortality worldwide (1), and the five-year survival rate remains extremely poor (2). Overall, ~75-85% of lung cancers cases are non-small cell lung cancer (NSCLC), which includes squamous cell carcinoma, adenocarcinoma and large cell carcinoma. The treatment of lung cancer involves the use of medical therapies such as surgery, radiation, chemotherapy and palliative care (3) in an attempt to successfully treat or reduce the adverse impact of malignant neoplasms originating in lung tissue. Chemotherapeutic agents are the main treatment measures for NSCLC, but the side-effects are usually difficult to tolerate (4).Fish oils are an excellent source of long-chain ω-3 polyunsaturated fatty acids (ω-3 PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Fish oil supplements are increasingly recognized by clinical studies to be useful for the treatment of a variety of human afflictions, including cancer (5). Numerous studies reveal evidence for the capability of ω-3 PUFAs to decrease proliferation, exert a pro-apoptotic effect and inhibit angiogenesis in several in vitro models of colon cancer (6-9).A previous study indicated that DHA and EPA inhibit the proliferation of A549 cells and induce apoptosis, with autophagy also being observed under transmission electron microscopy (10). Autophagy is a type of programmed cell death and it is an important process that is involved in various human pathologies. Previous studies suggest that autophagy is important in the regulation of cancer development and progression and also in determining the response of tumor cells to anticancer therapy (11)(12)(13)(14). Several cell signaling pathways are implicated in regulating autophagy, including the phosphatidyl inositol 3-kinase (PI3K)/Akt/...
DWF4 and CPD are key brassinosteroids (BRs) biosynthesis enzyme genes. To explore the function of Populus euphratica DWF4 (PeDWF4) and CPD (PeCPD), Arabidopsis thaliana transgenic lines (TLs) expressing PeDWF4, PeCPD or PeDWF4 plus PeCPD, namely PeDWF4-TL, PeCPD-TL and PeCP/DW-TL, were characterized. Compared with wild type (WT), the changes of both PeDWF4-TL and PeCPD-TL in plant heights, silique and hypocotyls lengths and seed yields were similar, but in bolting time and stem diameters, they were opposite. PeCP/DW-TL was more in plant heights and the lengths of primary root, silique, and fruit stalk, but less in silique numbers and seed yields than either PeDWF4-TL or PeCPD-TL. PeDWF4 and PeCPD specially expressed in PeDWF4-TL or PeCPDTL, and the transcription level of PeDWF4 was higher than that of PeCPD. In PeCP/DW-TL, their expressions were all relatively reduced. Additionally, the expression of PeDWF4 and PeCPD differentially made the expression levels of AtDWF4, AtCPD, AtBR6OX2, AtFLC, AtTCP1 and AtGA5 change in the TLs. The total BRs contents were PeDWF4-TL greater than PeCP/DW-TL greater than WT greater than PeCPD-TL. These results imply that PeDWF4 is functionally not exactly the same as PeCPD and there may be a synergistic and antagonistic effects in physiology between both of them in the regulation of plant growth and development.
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