Pro‑metastatic signaling of the trans fatty acid elaidic acid is associated with lipid rafts

Kishi, Satoru; Fujiwara‐Tani, Rina; Luo, Yi; Kawahara, Isao; Goto, Kei; Fujii, Kenichi; Ohmori, Hitoshi; Nakashima, Chie; Sasaki, Takuma; Kuniyasu, Hiroki

doi:10.3892/ol.2018.7817

Cited by 14 publications

(14 citation statements)

References 23 publications

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“…In this study, biglycan overexpression was frequently observed in DM-CRC. Our data also showed that insulin induced biglycan production, with synergistic effects observed with simultaneous treatment with high concentration of glucose and pro-tumorous fatty acids, linoleic acid and elaidic acid [15,16,[47][48][49][50][51]. Such high levels of insulin, glucose, and fatty acids are associated with diabetic condition.…”

Section: Discussionsupporting

confidence: 69%

Diabetes mellitus is associated with liver metastasis of colorectal cancer through production of biglycan-rich cancer stroma

et al. 2020

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High morbidity and mortality of cancer, especially colorectal cancer (CRC), in diabetic patients have been reported. In this study, we investigated the relationship between the presence of diabetes mellitus (blood hemoglobin A1C was 6.5% or higher at the time of diagnosis of CRC) and the progression and liver metastasis of CRC. Histopathological findings in the primary lesions, which were preferential to diabetes-complicated CRC (DM-CRC) and the liver metastasis, were also investigated. Of the 473 CRC patients who underwent curative surgical resection, 148 (31%) had diabetes. In DM-CRC cases, the stage was more advanced, with more cases in stage IV or postoperative disease recurrence. Histopathological findings correlated with liver metastasis in DM-CRC, including budding grade, perineural invasion, and myxomatous tumor stroma, and all were highly correlated with the stage. Additionally, myxomatous stroma showed the strongest correlation with liver metastasis in multivariate analysis. Myxomatous stroma in stage III cases correlated with liver recurrence. The myxomatous stroma was abundant in biglycan protein and contained numerous CD90-positive mesenchymal stem cells (MSCs). In human colon cancer cell line HT29, biglycan expression was induced by high sugar concentration, fatty acids, and insulin, and its contact co-culture with MSCs resulted in enhanced stemness and epithelial-mesenchymal transition phenotype. Thus, DM-CRC has higher malignant phenotypes compared to non-DM-CRC, and the involvement of diabetes-induced biglycan may act as a pathogenic factor.

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Section: Discussionsupporting

confidence: 69%

Diabetes mellitus is associated with liver metastasis of colorectal cancer through production of biglycan-rich cancer stroma

et al. 2020

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“…Moreover, they found that EA increased the resistance of these cells to 5-fluorouracil [ 41 ]. Pro-metastatic effects of EA in CRC have been associated with activation of EGFR signaling in cholesterol-rich lipid rafts [ 42 ], While, it was showed that the use of DHA with taxane drugs suppressed genes related to NF-κB. The results of this study suggest that the use of DHA with a drug from the taxane group weakens the resistance of cancer cells to taxanes and increases their cytotoxic effect on prostate cancer cells [ 43 ].…”

Section: Discussionmentioning

confidence: 93%

The Effect of Fatty Acids on Ciprofloxacin Cytotoxic Activity in Prostate Cancer Cell Lines—Does Lipid Component Enhance Anticancer Ciprofloxacin Potential?

Chrzanowska

Olejarz

Kubiak-Tomaszewska

et al. 2022

Cancers

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Purpose: To assess cytotoxic effect of ciprofloxacin conjugates with fatty acids on prostate cancer cells (LNCaP and DU-145) with different hormone sensitivity, based on previous promising results from the PC3 cells. Methods: Cytotoxicity were estimated using MTT and LDH tests, whereas its mechanisms were estimated by apoptosis and IL-6 assays. The intensity of proteins involved in lipid metabolism was determined using ML-CS assay. Results: The hormone insensitive DU-145 cells were more vulnerable than the hormone sensitive LNCaP cells. The IC50 values for oleic (4), elaidic (5) and docosahexaenoic acid (8) conjugates were 20.2 µM, 17.8 µM and 16.5 µM, respectively, in DU-145 cells, whereas in LNCaP cells IC50 exceeded 20 µM. The strong conjugate cytotoxicity was confirmed in the LDH test, the highest (70.8%) for compound (5) and 64.2% for compound (8) in DU-145 cells. This effect was weaker for LNCaP cells (around 60%). The cytotoxic effect of unconjugated ciprofloxacin and fatty acids was weaker. The early apoptosis was predominant in LNCaP while in DU-145 cells both early and late apoptosis was induced. The tested conjugates decreased IL-6 release in both cancer cell lines by almost 50%. Proteomic analysis indicated influence of the ciprofloxacin conjugates on lipid metabolic proteins in prostatic cancer. Conclusion: Our findings suggested the cytotoxic potential of ciprofloxacin conjugates with reduction in proteins involved in prostate cancer progress.

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“…Our data implicate for the first time a role for cholesterol synthesis in ADM. Although the mechanisms through which cholesterol acts remain to be determined, possibilities include regulation of hedgehog signaling (46), which has been implicated in acinar cell regeneration after injury and early carcinogenesis (47,48), or lipid rafts (49), which are cholesterol-rich and promote EGFR signaling (50)(51)(52). Cholesterol has also recently been shown to stimulate proliferation of intestinal stem cells and to promote tumor formation (53), suggesting that cholesterol metabolism might play similar roles in colon and pancreatic carcinogenesis.…”

Section: Researchmentioning

confidence: 99%

Acetyl-CoA Metabolism Supports Multistep Pancreatic Tumorigenesis

et al. 2019

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Pancreatic ductal adenocarcinoma (PDA) has a poor prognosis, and new strategies for prevention and treatment are urgently needed. We previously reported that histone H4 acetylation is elevated in pancreatic acinar cells harboring Kras mutations prior to the appearance of premalignant lesions. Because acetyl-CoA abundance regulates global histone acetylation, we hypothesized that altered acetyl-CoA metabolism might contribute to metabolic or epigenetic alterations that promote tumorigenesis. We found that acetyl-CoA abundance is elevated in KRAS -mutant acinar cells and that its use in the mevalonate pathway supports acinar-to-ductal metaplasia (ADM). Pancreas-specifi c loss of the acetyl-CoA-producing enzyme ATP-citrate lyase (ACLY) accordingly suppresses ADM and tumor formation. In PDA cells, growth factors promote AKT-ACLY signaling and histone acetylation, and both cell proliferation and tumor growth can be suppressed by concurrent BET inhibition and statin treatment. Thus, KRAS-driven metabolic alterations promote acinar cell plasticity and tumor development, and targeting acetyl-CoA-dependent processes exerts anticancer effects. SIGNIFICANCE :Pancreatic cancer is among the deadliest of human malignancies. We identify a key role for the metabolic enzyme ACLY, which produces acetyl-CoA, in pancreatic carcinogenesis. The data suggest that acetyl-CoA use for histone acetylation and in the mevalonate pathway facilitates cell plasticity and proliferation, suggesting potential to target these pathways. Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): A. Carrer, S. Trefely,

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Pro‑metastatic signaling of the trans fatty acid elaidic acid is associated with lipid rafts

Cited by 14 publications

References 23 publications

Diabetes mellitus is associated with liver metastasis of colorectal cancer through production of biglycan-rich cancer stroma

Diabetes mellitus is associated with liver metastasis of colorectal cancer through production of biglycan-rich cancer stroma

The Effect of Fatty Acids on Ciprofloxacin Cytotoxic Activity in Prostate Cancer Cell Lines—Does Lipid Component Enhance Anticancer Ciprofloxacin Potential?

Acetyl-CoA Metabolism Supports Multistep Pancreatic Tumorigenesis

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