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In Vivo (Athens, Greece) 2023Breast cancer stem cells (BCSCs) are involved in the development of breast cancer and contribute to therapeutic resistance. This study aimed to investigate the...
BACKGROUND/AIM
Breast cancer stem cells (BCSCs) are involved in the development of breast cancer and contribute to therapeutic resistance. This study aimed to investigate the anticancer stem cell (CSC) mechanism of 13-Oxo-9Z,11E-octadecadienoic acid (13-Oxo-ODE) as a potent CSC inhibitor in breast cancer.
MATERIALS AND METHODS
The effects of 13-Oxo-ODE on BCSCs were evaluated using a mammosphere formation assay, CD44/CD24 analysis, aldehyde dehydrogenase (ALDH) assay, apoptosis assay, quantitative real-time PCR, and western blotting.
RESULTS
We found that 13-Oxo-ODE suppressed cell proliferation, CSC formation, and mammosphere proliferation and increased apoptosis of BCSCs. Additionally, 13-Oxo-ODE reduced the subpopulation of CD44/CD24 cells and ALDH expression. Furthermore, 13-Oxo-ODE decreased c-myc gene expression. These results suggest that 13-Oxo-ODE has potential as a natural inhibitor targeting BCSCs through the degradation of c-Myc.
CONCLUSION
In summary, 13-Oxo-ODE induced CSC death possibly through reduced c-Myc expression, making it a promising natural inhibitor of BCSCs.
Topics: Humans; Female; Breast Neoplasms; Cell Proliferation; Neoplastic Stem Cells; Cell Line, Tumor
PubMed: 37103085
DOI: 10.21873/invivo.13183 -
[Effects of octadecadienoic acid on proliferation and apoptosis of glioma cells and its mechanisms].Zhongguo Ying Yong Sheng Li Xue Za Zhi... Sep 2022To study the effects of octadecadienoic acid (ODA) on the proliferation and apoptosis of glioma cells and its mechanisms.
OBJECTIVE
To study the effects of octadecadienoic acid (ODA) on the proliferation and apoptosis of glioma cells and its mechanisms.
METHODS
Cultured human glioma cells (cell density 2×10 cells/L) were divided into solvent control group (DMSO, 30 μl/L), 5-FU group (10 mg/L) and octadecadienic acid groups (0.3, 0.6 and 1.2 mg/L groups). The toxicity of ODA on glioma cells was detected by trypan blue and thiazolium blue (MTT). The expression levels of P53, PI3K, P21, PKB/Akt and Caspase-9 in glioma cells were determined by enzyme-linked immunosorbent assay (ELISA).
RESULTS
① Cell count under optical microscope showed that the inhibition rate of cell proliferation in ODA low, medium and high dose groups and 5-FU group was significantly higher than that in the solvent control group (<0.01), but there was no statistical significance compared with the 5-FU group (>0.05). ② MTT assay showed that the inhibition rate of cell proliferation was increased significantly in ODA low, medium and high dose groups and 5-FU groups (<0.01), compared with the solvent control group. Compared with 5-FU group, the inhibition rate of cell proliferation was increased significantly only in ODA high dose group (<0.01). ③ The number of G/G phase cells in ODA low, medium and high dose groups and 5-FU group were increased significantly (<0.05, <0.01), the number of G/M phase cells were decreased significantly (<0.01), and the apoptosis rate was increased significantly (<0.01),compared with the solvent control group. Compared with the 5-FU group, the number of cells in G/M phase was decreased significantly (<0.01) and the apoptosis rate was increased significantly (<0.01) in ODA high dose group. ④ ELISA test results showed that the protein expression levels of P53, PI3K and PKB/Akt in ODA low , medium and high dose groups and 5-FU group were significantly lower than those in solvent control group (all <0.01), but the protein expression levels in ODA high dose group were significantly lower than those in 5-FU group (<0.01). The protein expression levels of P21 and caspase-9 in ODA low , medium and high dose groups and 5-FU group were significantly higher than those in solvent control group (<0.05, <0.01), but the protein expression levels in ODA high dose group were significantly higher than those in 5-Fu group (<0.01).
CONCLUSION
ODA can significantly inhibit the proliferation and promote apoptosis of glioma cells. The mechanisms are related to up-regulating the levels of P21 and caspase-9 to promote apoptosis, down-regulating the levels of P53, PI3K and PKB/Akt to inhibit the cell division cycle, and reducing the activity of PI3K-Akt signal transduction pathway.
Topics: Humans; Proto-Oncogene Proteins c-akt; Caspase 9; Tumor Suppressor Protein p53; Phosphatidylinositol 3-Kinases; Glioma; Apoptosis; Cell Proliferation; Cell Line, Tumor; Fluorouracil
PubMed: 37088747
DOI: 10.12047/j.cjap.6271.2022.081 -
Lipids Mar 2017Many uncommon non-methylene-interrupted fatty acids (NMI FA) are present in limpet gonads, but their biological properties remain unknown. To investigate new biological...
Many uncommon non-methylene-interrupted fatty acids (NMI FA) are present in limpet gonads, but their biological properties remain unknown. To investigate new biological effects of naturally occurring NMI FA in eukaryotic cells, the biological activities of structurally analogous (4Z,15Z)-octadecadienoic acid (1), (9Z,20Z)-tricosadienoic acid (2), and (12Z,23Z)-hexacosadienoic acid (3) were examined by using a yeast-based drug-screening system using the Ca-sensitive mutant strain, Saccharomyces cerevisiae (zds1Δ erg3Δ pdr1Δ pdr3Δ). Among 1-3, 1 showed restored growth activity at a dose of 80 µg/disc in the mutant yeast strain. This phenotype suggests that 1 suppresses Ca-signaling of the mutant yeast through inhibition of glycogen synthase kinase-3β (GSK-3β) or calcineurin pathways or both. From this result, the inhibitory activity of 1-3 against GSK-3β was further determined. 1-3 showed potent inhibitory activity against GSK-3β with IC values ranging from 8.7 to 21.9 µM. Inhibition of GSK-3β reduces gene expression of the gluconeogenic key enzymes in liver, so we analyzed glucose production in rat hepatoma H4IIE cells to assess GSK-3β inhibitory activity of 1-3. Acid 1 inhibited glucose production at 25 µM in H4IIE cells. Our results would open up new possibilities for an anti-diabetic effect of 1 and might provide important insights into understanding the biological properties of naturally occurring NMI FA.
Topics: Animals; Calcineurin; Calcium; Cell Line; Cell Survival; Drug Evaluation, Preclinical; Fatty Acids, Unsaturated; Glucose; Glycogen Synthase Kinase 3 beta; HL-60 Cells; Humans; Rats; Saccharomyces cerevisiae
PubMed: 28194557
DOI: 10.1007/s11745-017-4236-3 -
Molecules (Basel, Switzerland) Oct 2020Cancer stem cells have certain characteristics, such as self-renewal, differentiation, and drug resistance, which are related to tumor progression, maintenance,...
Cancer stem cells have certain characteristics, such as self-renewal, differentiation, and drug resistance, which are related to tumor progression, maintenance, recurrence, and metastasis. In our study, we targeted breast cancer stem cells (BCSCs) using a natural compound, coriolic acid, from L. This compound was isolated by mammosphere formation inhibition bioassay-guided fractionation and identified by using NMR spectroscopy and electrospray ionization mass spectrometry. Coriolic acid inhibited the formation of mammospheres and induced BCSC apoptosis. It also decreased the subpopulation of CD44/CD24 cells, a cancer stem cell (CSC) phenotype, and specific genes related to CSCs, such as , and . Coriolic acid decreased the transcriptional and translational levels of the c-Myc gene, which is a CSC survival factor. These results indicated that coriolic acid could be a novel compound to target BCSCs via regulation of c-Myc.
Topics: Apoptosis; Breast Neoplasms; Chenopodiaceae; Fatty Acids, Unsaturated; Gene Expression Regulation, Neoplastic; Humans; MCF-7 Cells; Neoplastic Stem Cells; Proto-Oncogene Proteins c-myc
PubMed: 33114669
DOI: 10.3390/molecules25214950 -
Progress in Lipid Research Sep 1996
Review
Biosynthesis, metabolization and biological importance of the primary 15-lipoxygenase metabolites 15-hydro(pero)XY-5Z,8Z,11Z,13E-eicosatetraenoic acid and 13-hydro(pero)XY-9Z,11E-octadecadienoic acid.
Topics: Animals; Arteriosclerosis; Cardiovascular System; Cornea; Erythropoiesis; Leukotrienes; Linoleic Acids; Lipid Peroxides; Mammals; Skin; Vasoconstrictor Agents
PubMed: 9082450
DOI: 10.1016/s0163-7827(96)00008-2 -
Biochemical and Biophysical Research... Sep 2020We evaluated the effect of gut bacterial metabolites of polyunsaturated fatty acids on inflammation and found that 10-oxo-cis-6,trans-11-octadecadienoic acid (γKetoC)...
We evaluated the effect of gut bacterial metabolites of polyunsaturated fatty acids on inflammation and found that 10-oxo-cis-6,trans-11-octadecadienoic acid (γKetoC) strikingly suppressed LPS-induced IL-6 release from bone marrow-derived macrophages (BMMs), which was accompanied by reduced mRNA expression of Il6, TNF, and Il1b. γKetoC decreased the cAMP concentration in BMMs, suggesting that γKetoC stimulated G protein-coupled receptors. A Gq agonist significantly suppressed LPS-induced IL-6 expression in BMMs, whereas a Gi inhibitor partially abrogated γKetoC-mediated IL-6 suppression. Cytosolic Ca was markedly increased by γKetoC, which was partly but not fully abrogated by an ion channel inhibitor. Taken together, these data suggest that γKetoC suppresses inflammatory cytokine expression in macrophages primarily through Gq and partially through Gi. γKetoC suppressed osteoclast development and IL-6 expression in synovial fibroblasts from rheumatoid arthritis (RA) patients, suggesting the beneficial effect of γKetoC on the prevention or treatment of RA.
Topics: Animals; Arthritis, Rheumatoid; Cell Line; Cells, Cultured; Cytokines; Fatty Acids, Unsaturated; Female; Gastrointestinal Microbiome; Humans; Inflammation; Lactobacillales; Macrophages; Mice; Mice, Inbred C57BL; Monocytes; Protective Factors; RAW 264.7 Cells
PubMed: 32828309
DOI: 10.1016/j.bbrc.2020.07.006 -
Scientific Reports Feb 2022Dysregulation of circadian rhythm can cause nocturia. Levels of fatty acid metabolites, such as palmitoylethanolamide (PEA), 9-hydroxy-10E,12Z-octadecadienoic acid...
Dysregulation of circadian rhythm can cause nocturia. Levels of fatty acid metabolites, such as palmitoylethanolamide (PEA), 9-hydroxy-10E,12Z-octadecadienoic acid (9-HODE), and 4-hydroxy-5E,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid (4-HDoHE), are higher in the serum of patients with nocturia; however, the reason remains unknown. Here, we investigated the circadian rhythm of fatty acid metabolites and their effect on voiding in mice. WT and Clock mutant (Clock) mice, a model for nocturia with circadian rhythm disorder, were used. Levels of serum PEA, 9-HODE, and 4-HDoHEl were measured every 8 h using LC/MS. Voiding pattern was recorded using metabolic cages after administration of PEA, 9-HODE, and 4-HDoHE to WT mice. Levels of serum PEA and 9-HODE fluctuated with circadian rhythm in WT mice, which were lower during the light phase. In contrast, circadian PEA and 9-HODE level deteriorated or retreated in Clock mice. Levels of serum PEA, 9-HODE, and 4-HDoHE were higher in Clock than in WT mice. Voiding frequency increased in PEA- and 4-HDoHE-administered mice. Bladder capacity decreased in PEA-administered mice. The changes of these bladder functions in mice were similar to those in elderly humans with nocturia. These findings highlighted the novel effect of lipids on the pathology of nocturia. These may be used for development of biomarkers and better therapies for nocturia.
Topics: Amides; Animals; CLOCK Proteins; Circadian Rhythm; Disease Models, Animal; Docosahexaenoic Acids; Ethanolamines; Fatty Acids; Injections, Intraperitoneal; Linoleic Acids, Conjugated; Male; Mice, Inbred C57BL; Nocturia; Palmitic Acids; Photoperiod; Urinary Bladder; Urination; Mice
PubMed: 35197540
DOI: 10.1038/s41598-022-07096-5 -
Obesity Research & Clinical Practice 2013Conjugated linoleic acid (CLA), which is a generic term to describe isomers of octadecadienoic acid, has been reported to exert various beneficial physiological effects.... (Review)
Review
Conjugated linoleic acid (CLA), which is a generic term to describe isomers of octadecadienoic acid, has been reported to exert various beneficial physiological effects. Accumulating data show that CLA, especially trans10, cis12 (t10, c12)-CLA, has a potent body fat-reducing effect, which is prominent in mice and to a lesser extent rats. In addition, several clinical studies have demonstrated the body fat- and weight-reducing effect of CLA in humans. However, t10, c12-CLA evokes severe lipodystrophy in mice that results in impaired glucose metabolism. Therefore, while CLA is a promising agent for the amelioration of obesity and obesity-related diseases, it is important to establish its safety prior to common use in humans. In addition, it is important to elucidate the details of the molecular mechanisms of CLA. Here, we focus on the response of adipocyte to CLA.
Topics: Adipocytes; Adipokines; Adipose Tissue; Animals; Blood Glucose; Eicosanoids; Humans; Insulin Resistance; Linoleic Acids, Conjugated; Lipid Metabolism; PPAR gamma; Stress, Physiological
PubMed: 24455759
DOI: 10.1016/j.orcp.2013.04.002 -
The American Journal of Clinical... May 2007Several observational studies indicate that trans isomeric fatty acids may interfere with the metabolism of essential fatty acids in the human organism.
BACKGROUND
Several observational studies indicate that trans isomeric fatty acids may interfere with the metabolism of essential fatty acids in the human organism.
OBJECTIVE
The objective was to investigate the relation between trans fatty acids and long-chain polyunsaturates in mature human milk.
DESIGN
Human milk samples (n=769) were obtained at the 6th week of lactation from mothers participating in a birth cohort study in Germany. The fatty acid composition of the milk samples was measured by high-resolution capillary gas-liquid chromatography.
RESULTS
trans Octadecenoic and trans octadecadienoic acids were inversely correlated with linoleic acid (r=-0.32 and -0.33, P<0.0001 for both), alpha-linolenic acid (r=-0.35 and -0.27, P<0.0001), arachidonic acid (r=-0.60 and -0.47, P<0.0001), and docosahexaenoic acid (r=-0.51 and -0.33, P<0.0001). In contrast, no inverse correlations were observed between trans hexadecenoic acid and polyunsaturated fatty acids.
CONCLUSIONS
The data obtained in the present study suggest that the availability of 18-carbon trans isomeric fatty acids may be inversely related to the availability of long-chain polyunsaturated fatty acids in mature human milk.
Topics: Adult; Chromatography, Gas; Cohort Studies; Fatty Acids, Essential; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Female; Germany; Humans; Isomerism; Linolenic Acids; Milk, Human; Postpartum Period; Stearic Acids; Trans Fatty Acids; alpha-Linolenic Acid
PubMed: 17490969
DOI: 10.1093/ajcn/85.5.1320 -
The Journal of Dermatology Jun 2018
Topics: Cell Line; Electric Impedance; Epidermal Cells; Epidermis; Humans; Keratinocytes; Linoleic Acids; Linoleic Acids, Conjugated
PubMed: 29864226
DOI: 10.1111/1346-8138.14289