Docoxahexaenoic Acid Induces Apoptosis of Pancreatic Cancer Cells by Suppressing Activation of STAT3 and NF-κB

Park, Mirae; Lim, Joo Weon; Kim, Hye Young

doi:10.3390/nu10111621

Cited by 22 publications

(15 citation statements)

References 49 publications

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“…DHA was also reported to enhance the oxaliplatin-induced decrease in cell viability and an increase in autophagy via ER stress/Sesn2 pathway in colorectal cancer cell lines both in vitro and in vivo [231]. DHA induced apoptosis of PANC-1 pancreatic cancer cells by suppressing the STAT3/ NF-κB -cyclin D1/survivin axis [232]. DHA inhibited proliferation and progression of A549 non-small cell lung cancer cells through ROS-mediated inactivation of the PI3K/Akt pathway [233], and also through the miR-138-5p/FOXC1 pathway in A549 and H1299 human lung cancer cell lines and LLC murine lung cancer cells [234].…”

Section: ω-3 Pufasmentioning

confidence: 96%

Dietary Fat and Cancer—Which Is Good, Which Is Bad, and the Body of Evidence

Bojková

Winklewski

Wszędybył-Winklewska

2020

IJMS

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A high-fat diet (HFD) induces changes in gut microbiota leading to activation of pro-inflammatory pathways, and obesity, as a consequence of overnutrition, exacerbates inflammation, a known risk factor not only for cancer. However, experimental data showed that the composition of dietary fat has a greater impact on the pathogenesis of cancer than the total fat content in isocaloric diets. Similarly, human studies did not prove that a decrease in total fat intake is an effective strategy to combat cancer. Saturated fat has long been considered as harmful, but the current consensus is that moderate intake of saturated fatty acids (SFAs), including palmitic acid (PA), does not pose a health risk within a balanced diet. In regard to monounsaturated fat, plant sources are recommended. The consumption of plant monounsaturated fatty acids (MUFAs), particularly from olive oil, has been associated with lower cancer risk. Similarly, the replacement of animal MUFAs with plant MUFAs decreased cancer mortality. The impact of polyunsaturated fatty acids (PUFAs) on cancer risk depends on the ratio between ω-6 and ω-3 PUFAs. In vivo data showed stimulatory effects of ω-6 PUFAs on tumour growth while ω-3 PUFAs were protective, but the results of human studies were not as promising as indicated in preclinical reports. As for trans FAs (TFAs), experimental data mostly showed opposite effects of industrially produced and natural TFAs, with the latter being protective against cancer progression, but human data are mixed, and no clear conclusion can be made. Further studies are warranted to establish the role of FAs in the control of cell growth in order to find an effective strategy for cancer prevention/treatment.

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Section: ω-3 Pufasmentioning

confidence: 96%

Dietary Fat and Cancer—Which Is Good, Which Is Bad, and the Body of Evidence

Bojková

Winklewski

Wszędybył-Winklewska

2020

IJMS

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“…Compounds that prevent post-translational modification of Ras and its plasma membrane targeting are likely to inhibit oncogenic Ras signaling [47,49]. Previous reports from our lab and others suggest that PUFAs alter the plasma membrane binding domains of Ras to disrupt signaling [26,39,40,52,53]. Since Ras proteins are central to several signaling cascades, downregulation of the RAS genes observed in the gene expression study and suppressing expression of all the Ras isoforms studied in the western blot analysis, are expected to impact critical oncogenic pathways.…”

Section: Discussionmentioning

confidence: 93%

Diclofenac Enhances Docosahexaenoic Acid-Induced Apoptosis in Vitro in Lung Cancer Cells

Poku

Jones

Baren

et al. 2020

Cancers

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Polyunsaturated fatty acids (PUFAs) and non-steroidal anti-inflammatory drugs (NSAIDs) show anticancer activities through diverse molecular mechanisms. However, the anticancer capacities of either PUFAs or NSAIDs alone is limited. We examined whether combining NSAIDs with docosahexaenoic (DHA), commonly derived from fish oils, would possibly synergize their anticancer activity. We determined the viability of lung cancer cell lines (NCI-H1573, A549, NCI-H1299, and NCI-H1975) after exposure to DHA and various NSAIDs. We further conducted cell apoptosis assays and analyzed apoptosis-associated proteins and some key proteins in the RAS/MEK/ERK and PI3K/Akt pathways using western blot analysis. We also determined the impact of the treatment on the expression of inducible cancer-related genes using nCounter PanCancer Pathways gene expression analysis. The results showed that the combination of DHA and NSAIDs increased suppression of cell viability in all the lung cancer cell lines tested compared to each of the compounds used alone, with diclofenac being the most potent NSAID tested. This synergistic effect is especially significant in A549 and NCI-H1573 cells. The combination treatment was more effective at inhibiting clonogenic cell growth and anchorage-independent growth in soft agar, inducing caspase-dependent apoptosis, and altering expression of critical proteins in the RAS/MEK/ERK and PI3K/Akt pathways. The data from this study demonstrate that DHA combined with low dose diclofenac provides greater anticancer potential, which can be further developed for chemoprevention and adjunct therapy in lung cancer.

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“…Indeed, n-3 PUFAs induce apoptosis and suppress cell proliferation in KRAS -mutant-derived pancreas nestin-expressing HPNE- KRAS G12D cells both in vitro and in vivo by reducing AKT phosphorylation [ 28 ]. A recent paper reported that DHA promotes the cell apoptosis of PANC-1 pancreatic cancer cells by inducing DNA fragmentation, activating caspase-3, and increasing the ratio of Bax/Bcl-2 via downregulating STAT3/nuclear factor (NF)-κB/cyclin D1 signaling [ 29 ]. On the other hand, EPA treatment of adipocytes reduces adipocyte-secreted factors, thus inhibiting breast cancer cell inflammation and migration [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Eicosapentaenoic Acid Inhibits KRAS Mutant Pancreatic Cancer Cell Growth by Suppressing Hepassocin Expression and STAT3 Phosphorylation

Chiu,

Hsu,

Yeh

et al. 2021

Biomolecules

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Background: The oncogenic Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation was reported to be the signature genetic event in most cases of pancreatic ductal adenocarcinoma (PDAC). Hepassocin (HPS/FGL1) is involved in regulating lipid metabolism and the progression of several cancer types; however, the underlying mechanism of HPS/FGL1 in the KRAS mutant PDAC cells undergoing eicosapentaenoic acid (EPA) treatment remains unclear. Methods: We measured HPS/FGL1 protein expressions in a human pancreatic ductal epithelial (HPNE) normal pancreas cell line, a KRAS-wild-type PDAC cell line (BxPC-3), and KRAS-mutant PDAC cell lines (PANC-1, MIA PaCa-2, and SUIT-2) by Western blot methods. HEK293T cells were transiently transfected with corresponding KRAS-expressing plasmids to examine the level of HPS expression with KRAS activation. We knocked-down HPS/FGL1 using lentiviral vectors in SUIT-2 cells and measured the cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clonogenicity assays. Furthermore, a lipidomic analysis was performed to profile changes in lipid metabolism after HPS/FGL1 knockdown. Results: We found that the HPS/FGL1 level was significantly upregulated in KRAS-mutated PDAC cells and was involved in KRAS/phosphorylated (p)-signal transduction and activator of transcription 3 (STAT3) signaling, and the knockdown of HPS/FGL1 in SUIT-2 cells decreased cell proliferation through increasing G2/M cell cycle arrest and cyclin B1 expression. In addition, the knockdown of HPS/FGL1 in SUIT-2 cells significantly increased omega-3 polyunsaturated fatty acids (PUFAs) and EPA production but not docosahexaenoic acid (DHA). Moreover, EPA treatment in SUIT-2 cells reduced the expression of de novo lipogenic protein, acetyl coenzyme A carboxylase (ACC)-1, and decreased p-STAT3 and HPS/FGL1 expressions, resulting in the suppression of cell viability. Conclusions: Results of this study indicate that HPS is highly expressed by KRAS-mutated PDAC cells, and HPS/FGL1 plays a crucial role in altering lipid metabolism and increasing cell growth in pancreatic cancer. EPA supplements could potentially inhibit or reduce ACC-1-involved lipogenesis and HPS/FGL1-mediated cell survival in KRAS-mutated pancreatic cancer cells.

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Docoxahexaenoic Acid Induces Apoptosis of Pancreatic Cancer Cells by Suppressing Activation of STAT3 and NF-κB

Cited by 22 publications

References 49 publications

Dietary Fat and Cancer—Which Is Good, Which Is Bad, and the Body of Evidence

Dietary Fat and Cancer—Which Is Good, Which Is Bad, and the Body of Evidence

Diclofenac Enhances Docosahexaenoic Acid-Induced Apoptosis in Vitro in Lung Cancer Cells

Eicosapentaenoic Acid Inhibits KRAS Mutant Pancreatic Cancer Cell Growth by Suppressing Hepassocin Expression and STAT3 Phosphorylation

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