Fatty Acid Composition of Precancerous Cervical Lesions and Cervical Cancer Tissues (original) (raw)
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Cytotoxic action of cis-unsaturated fatty acids on human cervical carcinoma (HeLa) cells in vitro
Prostaglandins, Leukotrienes and Essential Fatty Acids, 1995
The effect of n-3 and n-6 fatty acids (FAs) on the growth of human cervical carcinoma (HeLa) cells was studied. Of all the FAs tested, docosahexaenoic acid (DHA, 22:6 n-3) and eicosapentaenoic acid (EPA, 20:5 n-3) were found to be the most potent in their cytotoxic action on HeLa cells and the potency of various fatty acids with regard to their cytotoxic action was as follows: DHA > EPA > dihomo-gamma-linolenic acid (DGLA) = gamma-linolenic acid (GLA) > linoleic acid (LA) > arachidonic acid (AA) > alpha-linolenic acid (ALA). The cycloxygenase inhibitor indomethacin, the lipoxygenase inhibitor nordihydroguaretic acid (NDGA), the antioxidants vitamin E, butylated hydroxyanisole (BHA), and butylated hydroxytoluene (BHT), the superoxide anion quencher superoxide dismutase (SOD), the hydroxyl and hydrogen peroxide quenchers mannitol and catalase, respectively, and the calmodulin antagonists trifluoperazine (TFP) and chlorpromazine (CPZ) could all block the cytotoxic action of GLA, which was used as a representative cytotoxic FA, on HeLa cells. On the other hand, copper and iron salts and buthionine sulfoxamine, a glutathione (GSH) depletor, potentiated the cytotoxic action of suboptimal doses of GLA. GLA-induced radical generation and lipid peroxidation in HeLa cells could be blocked by indomethacin, NDGA and calmodulin antagonists. The cytotoxic action of cisunsaturated fatty acids (c-UFAs) is not dependent on the alteration in the protein kinase C levels since no alteration in the diacylglycerol levels was observed. Hydroxy and hydroperoxy products of GLA were found to be toxic to HeLa cells, whereas prostaglandin (PG)E1, PGF2a, and prostacyclin stimulated cell growth. From these results, it is evident that radicals are the modulators of the cytotoxic action of c-UFAs, that their formation is a calmodulin-dependent process, and that lipoxygenase products may mediate the tumoricidal action of FAs.
ifferent Fatty Acid Composition Between ormal and Malignant Cell Lines
1999
Twentyeight fatty aclds (C8:O to C24:ln-9) were measured by gas chromattography In four normal cell lines (C3H/lOT1/2, CCD18Co, CCD25SK and CCD 37Lu) an# seven cancer cell llnes ( M I , Caov-3, LS-180, PC3, SK-MEL-28, SK-MES-l and U-87 MG). Results show that C20:4 n-6, C24:0, C24:l n-9, Polyunsaturated fatty aclds (PUFA'S) and ratlos of C20:4 n-6 to C20:5 m3 and C16:O to C18:l n-9 and steatlc to olelc (SA/OA) were lower In the cancer cell llnes than In their normal courterparts. All cancer cell llnes had SA/OA ratlos lower than 0.7 while normal cell llnes had ratlos greater than 0.7 (p<0.05). In addition, the ratlos of total saturated fatty aclds (SFA) to PUFA'S and the concentration of C18:l rr 9, Cl8:2 n-6, C20:0, C20:2 n-6, C20:5 n-3 were higher In cancer cell llnes as compared to normal cell llnes. A positive cottelation was detected between C16:O and longer SFA'S (r=+0.511, p<0.05) In normal cell llnes whereas a negative correlation (r=0.608, ~ ~ 0 . 0 5 ) was...
Metabolic fate and effects of saturated and unsaturated fatty acids in Hep2 human larynx tumor cells
IUBMB Life, 1997
Previous studies have reported the presence of carnitine palmitoyltransferase 1 and II in tumor cells and the inhibitory effects of fatty acids on cell proliferation. The present work considered the metabolic fate of [14C] or [3HI-labeled fatty acids and their effects on cellular metabolism in Hep2 human larynx tumor cells.The rate of uptake of acetate was 45% of that of myristate, paimitate, oleate, iinoleate and arachidonate. However, acetate was rapidly metabolized within the cell as seen by its low rate of accumulation as non-esterified fatty acid, <5% of that of the other fatty acids. The incorporation of fatty acids into neutral lipid fractions showed palmitate and oleate primarily entered the phospholipid fraction, while linoleate and arachidonate entered equally the phospholipid and triacylglycerol fractions. Palmitate and oleate were oxidized to ~4CO2 at higher rates than linoleate and arachidonate, with arachidonate being the least oxidized of the unsaturated fatty acids. Acetate was oxidized at 10-30 fold higher rates than the other fatty acids. Palmitate, oleate, linoleate and arachidonate all had significant inhibitory effects on the rate of glucose utilization by Hep2 cells, ranging from 25-38% inhibition and were found to inhibit cell proliferation by 17-73%. These findings suggest that certain fatty acids not only play a structural role in cellular metabolism, but may also have a potential regulatory role in the glycolytic pathway of Hep2 cells.
Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA), 2001
Research on fatty acid metabolism in cultured human larynx tumor cells Hep2 was carried out.The cells were incubated with either a saturated (palmitic) or a polyunsaturated (linoleic, a-linolenic and eicosatrienoic (n-6)) radioactive fatty acid (0.66 mM, 24 h).The best incorporation capacity was observed in the linoleic acid followed by a-linolenic, palmitic and eicosatrienoic acids. All fatty acids tested were anabolized to higher derivatives within their own family. Palmitic acid was primarily monodesaturated rather than elongated, proving to have a very active D9 desaturase activity.With respect to polyunsaturated acid metabolism, the conversion of a-linolenic acid to higher homologs, although better than linoleic acid, occurred far less efficiently than that observed in other non-highly undifferentiated human tumor cells.This impairment in higher polyunsaturated fatty acid biosynthesis, reflected in the low levels of arachidonic acid in the fatty acid composition, would not reside in the D5 desaturation step since Hep2 cells can readily convert eicosatrienoic acid into arachidonic acid. Considering the potential regulatory role of specific polyunsaturated fatty acids in the cell proliferative control, the knowledge of the metabolism of fatty acids in this human tumor cell would be important for designing future experiments in order to clarify the mechanism involved in balance, proliferation and cell death.
Journal of Internal Medicine, 1989
Dietary fat has a positive correlation with cancers of the breast and colon and probably other types of cancer. In experimental tumour systems, linoleic acid (LA) has tumourpromoting effects that are mediated, in part, through eicosanoid production. The feeding of fish oil has resulted in decreased concentrations of LA and arachidonic (AA) and increased concentrations of n-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Both n-3 fatty acids antagonize the production of eicosanoids from AA. Recent reports indicate that marine n-3 fatty acids inhibit the development and growth of several experimental tumours. The effect of n-3 fatty acids on 16-a-hydroxylation of oestradiol, a putative biornarker for risk of breast cancer. was studied in 2 5 women at enhanced risk. The control group of 2 5 high-risk women received vegetable oil. After 4 months, the level of oestradiol 16-a-hydroxylation was significantly reduced in women receiving fish oil, but no change was detected in the control group. Although the precise mechanism of action is unclear, these data suggest that use of marine n-3 fatty acids as chemopreventive agents in high-risk women requires further investigation.
Changes in tissue fatty acid composition in murine malignancy and following anticancer therapy
British journal of cancer, 1992
We studied the mouse NC tumour, a subcutaneously transplanted adenocarcinoma originally of mammary origin. Measurements per g tissue were made of 17 fatty acids (FAs), the combined amounts of n-3, n-6, saturated, unsaturated, and total FAs, and of various FA ratios in the tumour, mammary tissue, spleen, liver and plasma. Compared with mammary tissue from normal mice, tumours of vehicle-treated controls had less of seven of the FAs and more of two FAs. Mice bearing the NC tumour often had changed (usually decreased) amounts of FAs in the 'normal' spleen, liver and plasma, but not in mammary tissue. Treatment with methotrexate (MTX) was studied alone and with indomethacin which can potentiate MTX cytotoxicity. Indomethacin 1.25 mg kg-1 (INDO) increased the amounts of 3/17 tumours FAs and the unsaturated FAs, but reduced 9/17 FAs, the saturated and the unsaturated FAs in 'normal' mammary tissue, and usually had no effect on the FAs of other tissues. MTX 2 or 4 mg kg-1 (...
Fatty acid synthase as a potential new therapeutic target for cervical cancer
Anais Da Academia Brasileira De Ciencias, 2022
Fatty acid synthase (FASN) is the rate-limiting enzyme for the de novo synthesis of fatty acids in the cytoplasm of tumour cells. Many tumour cells express high levels of FASN, and its expression is associated with a poorer prognosis. Cervical cancer is a major public health problem, representing the fourth most common cancer affecting women worldwide. To date, only a few in silico studies have correlated FASN expression with cervical cancer. This study aimed to investigate in vitro FASN expression in premalignant lesions and cervical cancer samples and the effects of a FASN inhibitor on cervical cancer cells. FASN expression was observed in all cervical cancer samples with increased expression at more advanced cervical cancer stages. The FASN inhibitor (orlistat) reduced the in vitro cell viability of cervical cancer cells (C-33A, ME-180, HeLa and SiHa) in a time-dependent manner and triggered apoptosis. FASN inhibitor also led to cell cycle arrest and autophagy. FASN may be a potential therapeutic target for cervical cancer, and medicinal chemists, pharmaceutical researchers and formulators should consider this fi nding in the development of new treatment approaches for this cancer type.
The Journal of Nutritional Biochemistry, 2001
The aim of this study was to analyze the effects of a polyunsaturated n-6 high-fat diet on rat DMBA-induced breast cancer at different stages of the carcinogenesis and to investigate if changes in the tumor fatty acid composition are one of the mechanisms by which dietary lipids could exert their effects. 14 fatty acids were evaluated in 6 lipid fractions. The results firstly showed that this high-fat diet stimulated the malignant mammary tumor growth, mainly all in the promotion group. The tumor lipid analysis indicated: 1) that each lipid fraction presented distinct major fatty acids (Ͼ5%) which were not the most abundant in the diet, except in the case of the triacylglicerides, suggesting the different resistance to dietary fatty acid modification of the tumor lipid fractions; 2) a higher arachidonic acid content in the fractions with less linoleic acid, above all in phospholipids, particularly in the phosphatidylethanolamine, indicating a different efficiency of conversion; 3) the three most abundant fatty acids in the dietary lipid (18:2n-6, 18:1n-9 and 16:0) were those which essentially displayed the differences between groups; thus, the high-fat diet changed the tumor lipid profile, increasing the 18:2n-6 relative content and decreasing that of the 18:1n-9; differences were significant in phosphatidylcholine, free fatty acids and triacylglycerides. Any change was obtained in the phosphatidylinositol. The greatest number of differences was found in the promotion group. Taken as a whole, our results suggest the different roles of lipid fractions in breast cancer cells and an association between cancer malignancy and the content of linoleic and oleic acids.
Background: Oxidative stress has been associated with cer-vical cancer. Our aim was to examine lipid peroxidation and the extent of oxidative stress in women diagnosed with different stages of cervical cancer in order to evaluate its potential role in the evolution of cancer. Methods: We measured the concentration of thiobarbituric acid reactive substances, activities of antioxidative enzymes and 8-hydroxy-2-deoxyguanosine in 153 subjects. En zyma-tic activity as well as TBARS concentration were measured spectrophotometrically, while 8-OHdG was determined by gas chromatography–mass spectrometry. PPatients were categorized: group II H-SIL; group III FIGO Ia-Ib and group IV FIGO IIa-IV. Results: Our results showed highly significant increase in the level of lipid peroxidation in group IV when com pared to the control group, group II and group III (p<0.001). Activity of superoxide dismutase was also significantly higher in group IV when compared to control group (p<0.01), group II (p<0.01) and group III (p<0.05). Activity of catalase was also significantly higher in group IV when compared to control group (p<0.005), group II (p<0.005) and group III (p<0.05). Activity of glutathione-S-transferase was also significantly higher in group IV when compared to control group (p<0.05), group II (p<0.05) and group III (p<0.05). Activities of glutathione peroxidase and glutathione reduc-tase showed no significant differences among the groups. Level of 8-OHdG was significantly higher in group IV than in the other groups (p<0.01). Conclusions: It can be concluded that oxidative stress is possibly involved in the pathogenesis of cervical cancer,