linoleic-acid and Urinary-Bladder-Neoplasms

Both n-6 and n-3 polyunsaturated fatty acids are dietary fats important for cell function, being involved in several physiologic and pathologic processes, such as tumorigenesis. Linoleic acid and conjugated linoleic acid, its geometrical and positional stereoisomer, were tested on several human tumor cell lines originating from different tissues and with different degrees of malignancy. This was to provide the widest possible view of the impact of dietary lipids on tumor development. While linoleic acid exerted different effects, ranging from inhibitory to neutral, even promoting growth, conjugated linoleic acid inhibited growth in all lines tested and was particularly effective against the more malignant cells, with the exception of mammary tumor cells, in which behavior was the opposite, the more malignant cell line being less affected. The inhibitory effect of conjugated linoleic acid on growth may be accompanied by different contributions from apoptosis and necrosis. The effects of conjugated linoleic acid on growth or death involved positive or negative variations in PPARs. The important observation is that a big increase of PPARalpha protein occurred in cells undergoing strong induction of apoptosis, whereas PPARbeta/delta protein decreased. Although PPARalpha and PPARbeta/delta seem to be correlated to execution of the apoptotic program, the modulation of PPARgamma appears to depend on the type of tumor cell, increasing as protein content, when inhibition of cell proliferation occurred. In conclusion, CLA may be regarded as a component of the diet that exerts antineoplastic activity and its effect may be antiproliferative or pro-apoptotic.

Topics: Antineoplastic Agents; Apoptosis; Breast Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Proliferation; Female; Gene Expression Regulation, Neoplastic; Glioblastoma; Humans; Linoleic Acid; Linoleic Acids, Conjugated; Liver Neoplasms; Necrosis; Neoplasms; Peroxisome Proliferator-Activated Receptors; PPAR alpha; PPAR delta; PPAR gamma; PPAR-beta; Urinary Bladder Neoplasms

The relationship between 15(S)-HETE and 13(S)-HODE from different human tumor cells exposed to n-6 and n-3 essential fatty acids (EFAs) and E-cadherin expression was studied. Colon cancer cells (HRT-18) exposed to gamma linoleic acid (18:3n-6, GLA) and eicosapentaenoic (20:5n-3, EPA) (50microM) showed an increased expression of E-cadherin. Breast cancer (MCF-7) exposed to EPA showed an increment whereas GLA had no effect on E-cadherin expression. No expression of E-cadherin was observed for urothelial cancer (T-24) after GLA or EPA treatment. Significant levels of 15(S)-HETE and 13(S)-HODE were detected after GLA or EPA treatment for all tumor lines. E-cadherin expression was inversely proportional to the 13(S)-HODE:15(S)-HETE ratio when cells were pretreated with GLA or EPA. Nevertheless, the liberation of these metabolites seems to be independent of the E-cadherin expression. The increase in the13(S)-HODE:15(S)-HETE correlates to a decrease in the expression of E-cadherin. Both factors may play a role in metastasis development.

Topics: Arachidonic Acid; Breast Neoplasms; Cadherins; Cell Differentiation; Colonic Neoplasms; Female; Humans; Hydroxyeicosatetraenoic Acids; Immunohistochemistry; Linoleic Acid; Linoleic Acids; Neoplasm Metastasis; Tumor Cells, Cultured; Urinary Bladder Neoplasms; Urothelium

Modifying effects of dietary administration of conjugated fatty acids from safflower oil (CFA-S), rich in conjugated linoleic acid, on major organs were examined in the post-initiation stage of a two-stage carcinogenesis model in female rats. Groups of 21 or 22 F344 female rats were treated sequentially with 2,2'-dihydroxy-di-n-propylnitosamine (intragastrically, i.g.), 7,12-dimethylbenz[a]anthracene (i.g.), 1,2-dimethylhydrazine (subcutaneously) and N-butyl-N-(4-hydroxybutyl)nitrosamine (in drinking water) during the first 3 weeks for initiation, and then administered diet containing 1 or 0.1% CFA-S for 33 weeks. Further groups of animals were treated with carcinogens or 1% CFA-S alone, or maintained as non-treated controls. All surviving animals were killed at week 36, and major organs were examined histopathologically for development of pre-neoplastic and neoplastic lesions. The 1 and 0.1% CFA-S treatment significantly decreased the incidence and multiplicity of mammary carcinomas, though a clear dose response was not observed. In the urinary bladder, the incidence of papillary or nodular hyperplasia but not tumors was significantly increased in the 1% CFA-S-treated group. The results indicate that low dose CFA-S may find application as a potent chemopreventor of mammary carcinogenesis.

Topics: 1,2-Dimethylhydrazine; 9,10-Dimethyl-1,2-benzanthracene; Animals; Body Weight; Butylhydroxybutylnitrosamine; Carcinogens; Dietary Supplements; Dose-Response Relationship, Drug; Fatty Acids; Female; Glutathione Transferase; Hyperplasia; Linoleic Acid; Mammary Neoplasms, Experimental; Neoplasms; Nitrosamines; Organ Size; Phosphorylation; Rats; Rats, Inbred F344; Rats, Sprague-Dawley; Safflower Oil; Time Factors; Urinary Bladder Neoplasms

Potential promoting effects of alpha-linolenic, linoleic and palmitic acids were investigated in a two-stage urinary bladder carcinogenesis model. In experiment 1, male F344 rats were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in their drinking water for 4 weeks and then basal diet containing 10% alpha-linolenic, 10% linoleic or 10% palmitic acid along with 0.2% butylated hydroxyanisole (BHA) as an antioxidant for 24 weeks. The development of tumors in the urinary bladder was not increased by treatment with any of the fatty acids. In experiment 2, male F344 rats were given 10% alpha-linolenic, 10% linoleic or 10% palmitic acid along with 0.2% BHA in their diet for 8 weeks without prior BBN treatment. The administration of fatty acids was not associated with any increase in the 5-bromo-2'-deoxyuridine labeling index of the urinary bladder epithelium. Serum and/or urine fatty acid levels increased in the cases of alpha-linolenic and linoleic acid treatments, but not with palmitic acid. Under the present experimental conditions neither the two polyunsaturated nor the one saturated fatty acid exerted any promoting effect on urinary bladder carcinogenesis.

Topics: alpha-Linolenic Acid; Animals; Butylated Hydroxyanisole; Butylhydroxybutylnitrosamine; Hyperplasia; Kidney; Linoleic Acid; Linoleic Acids; Male; Organ Size; Palmitic Acid; Palmitic Acids; Rats; Rats, Inbred F344; Urinary Bladder; Urinary Bladder Neoplasms