linoleic-acid and Melanoma

Topics: Adult; Aged; Ascorbic Acid; beta Carotene; Chocolate; Collagen; Curcuma; Diet, Healthy; Dietary Supplements; Female; Fibroblasts; Glycine max; Humans; Isoflavones; Linoleic Acid; Lutein; Lycopene; Melanoma; Middle Aged; Receptors, Calcitriol; Skin; Skin Aging; Skin Care; Sunlight; Tea; Vitamin D; Vitamin E

Rose Bengal (RB) is an anionic water-soluble xanthene dye, which used for many years to assess eye cornea and conjunctiva damage. RB showed strong absorption maxima (λmax) under visible light followed by UV-B and UV-A. RB under sunlight exposure showed a time-dependent photodegradation. Our results show that photosensitized RB generates (1)O2 via Type-II photodynamic pathway and induced DNA damage under sunlight/UV-R exposure. 2'dGuO degradation, micronuclei formation, and single- and double-strand breakage were the outcome of photogenotoxicity caused by RB. Quenching studies with NaN3 advocate the involvement of (1)O2 in RB photogenotoxicity. RB induced linoleic acid photoperoxidation, which was parallel to (1)O2-mediated DNA damage. Oxidative stress in A375 cell line (human melanoma cell line) was detected through DCF-DA assay. Photosensitized RB decreased maximum cellular viability under sunlight followed by UV-B and UV-A exposures. Apoptosis was detected as a pattern of cell death through the increased of caspase-3 activity, decreased mitochondrial membrane potential, and PS translocation through inner to outer plasma membrane. Increased cytosolic levels of Bax also advocate the apoptotic cell death. We propose a p53-mediated apoptosis via increased expression of Bax gene and protein. Thus, the exact mechanism behind RB phototoxicity was the involvement of (1)O2, which induced oxidative stress-mediated DNA and membrane damage, finally apoptotic cell death under natural sunlight exposure. The study suggests that after the use of RB, sunlight exposure may avoid to prevent from its harmful effects.

Topics: Caspase 3; Cell Line, Tumor; DNA Damage; Humans; Linoleic Acid; Melanoma; Membrane Potential, Mitochondrial; Microscopy, Electron, Transmission; Oxidation-Reduction; Pyrimidine Dimers; Reactive Oxygen Species; Rose Bengal; Sunlight

We investigated the association of melanoma risk with food consumption in a northern Italian population in which disease risk was shown to correlate with linoleic acid and soluble carbohydrates intake. We collected information regarding the habitual consumption of 188 food items in 59 patients with newly diagnosed cutaneous melanoma and 59 sex- and age-matched population controls. In the unadjusted analyses, the intake of several foodstuffs directly or inversely correlated with melanoma risk. In multivariate analysis adjusting for several potential confounders, risk correlated directly with vegetable oil intake and inversely with consumption of crispbreads and rusks. Overall, most of the food items rich in linoleic acid and soluble carbohydrates were unrelated to disease risk. Despite the limited statistical precision of the point estimates, these findings seem to indicate that consumption of specific foods may influence melanoma risk.

Topics: Case-Control Studies; Diet; Dietary Carbohydrates; Fatty Acids, Unsaturated; Female; Humans; Italy; Linoleic Acid; Male; Melanoma; Multivariate Analysis; Odds Ratio; Plant Oils; Risk Factors; Skin Neoplasms

Topics: Alcohol Drinking; Carotenoids; Case-Control Studies; Diet; Diet Surveys; Humans; Linoleic Acid; Melanoma; Micronutrients; Risk Factors; Skin Neoplasms; Sunlight; Vitamins

We aimed at examining the association between dietary constituents and risk of cutaneous melanoma.. In an area of northern Italy we recruited 59 newly diagnosed melanoma patients and 59 age- and sex-matched population controls, to whom we administered a validated semi-quantitative food-frequency questionnaire.. We found an excess risk of melanoma in subjects with a higher energy-adjusted intake of total polyunsaturated fatty acids and, in particular, of linoleic acid (relative risk = 2.16 for intake in the highest tertile compared with the lowest tertile, P for linear trend = 0.061). Conversely, disease risk was inversely associated with the consumption of soluble carbohydrates (relative risk = 0.34 for intake in the upper vs. the lowest tertile adjusting for total energy intake, P for linear trend = 0.046). No other dietary factors, including alcohol, vitamins and trace elements, correlated with melanoma risk. The association of melanoma risk with linoleic acid and soluble carbohydrates intakes was further strengthened in multivariate analysis, and when analysis was limited to females.. Overall, these results indicate that an excess energy-adjusted intake of linoleic acid and a lower consumption of soluble carbohydrates may increase melanoma risk.

Topics: Case-Control Studies; Dietary Carbohydrates; Fatty Acids, Unsaturated; Female; Humans; Italy; Linoleic Acid; Male; Melanoma; Middle Aged; Multivariate Analysis; Odds Ratio; Risk Factors; Skin Neoplasms; Surveys and Questionnaires

Fatty acids are common components of biological membranes that are known to play important roles in intracellular signaling. We report here a novel mechanism by which fatty acids regulate the degradation of tyrosinase, a critical enzyme associated with melanin biosynthesis in melanocytes and melanoma cells. Linoleic acid (unsaturated fatty acid, C18:2) accelerated the spontaneous degradation of tyrosinase, whereas palmitic acid (saturated fatty acid, C16:0) retarded the proteolysis. The linoleic acid-induced acceleration of tyrosinase degradation could be abrogated by inhibitors of proteasomes, the multicatalytic proteinase complexes that selectively degrade intracellular ubiquitinated proteins. Linoleic acid increased the ubiquitination of many cellular proteins, whereas palmitic acid decreased such ubiquitination, as compared with untreated controls, when a proteasome inhibitor was used to stabilize ubiquitinated proteins. Immunoprecipitation analysis also revealed that treatment with fatty acids modulated the ubiquitination of tyrosinase, i.e. linoleic acid increased the amount of ubiquitinated tyrosinase whereas, in contrast, palmitic acid decreased it. Furthermore, confocal immunomicroscopy showed that the colocalization of ubiquitin and tyrosinase was facilitated by linoleic acid and diminished by palmitic acid. Taken together, these data support the view that fatty acids regulate the ubiquitination of tyrosinase and are responsible for modulating the proteasomal degradation of tyrosinase. In broader terms, the function of the ubiquitin-proteasome pathway might be regulated physiologically, at least in part, by fatty acids within cellular membranes.

Topics: Animals; Blotting, Western; Cell Line, Tumor; Cycloheximide; Cysteine Endopeptidases; Dose-Response Relationship, Drug; Fatty Acids; Intracellular Membranes; Kinetics; Linoleic Acid; Melanocytes; Melanoma; Mice; Microscopy, Confocal; Microscopy, Fluorescence; Monophenol Monooxygenase; Multienzyme Complexes; Palmitic Acid; Pigmentation; Precipitin Tests; Proteasome Endopeptidase Complex; Protein Synthesis Inhibitors; Signal Transduction; Time Factors; Ubiquitin

Malignant melanoma has been one of the most rapidly increasing cancers within the United States with few modifiable risk factors. This study investigates risk related to dietary factors, which are potentially modifiable.. Newly diagnosed patients with melanoma (n = 502) were recruited from pigment lesion clinics and controls (n = 565) were recruited from outpatient clinics. To investigate the relationship between melanoma and dietary factors in this case-control study, study subjects were requested to complete a food frequency questionnaire, which assessed diet over the previous year. Using logistic regression, odds ratios (ORs) for melanoma were computed for nutrient and alcohol intake.. Persons in high versus low quintiles of energy-adjusted vitamin D, alpha-carotene, beta-carotene, cryptoxanthin, lutein, and lycopene had significantly reduced risk for melanoma (ORs < or = 0.67), which remained after adjustment for presence of dysplastic nevi, education, and skin response to repeated sun exposure. Addition of micronutrients from supplements did not add an additional reduction in risk. High alcohol consumption was associated with an increased risk for melanoma, which remained after adjustment for confounders [OR (95% confidence interval) in highest versus lowest quintiles, 1.65 (1.09-2.49)].. Diets consisting of foods rich in vitamin D and carotenoids and low in alcohol may be associated with a reduction in risk for melanoma. These analyses should be repeated in large, prospective studies.

Topics: Adult; Aged; Alcohol Drinking; Carotenoids; Case-Control Studies; Diet; Diet Surveys; Female; Humans; Linoleic Acid; Logistic Models; Male; Melanoma; Micronutrients; Middle Aged; Philadelphia; Risk Factors; San Francisco; Skin Neoplasms; Sunlight; Vitamins

Ayurveda, an ancient and comprehensive system of natural medicine, recommends regular topical application to the skin of sesame oil, above all other oils, as a health-promoting procedure. We examined the effect of sesame oil and several other vegetable oils and their major component fatty acids on the proliferation rate of human normal and malignant melanocytes growing at similar rates in serum-free media. We found that sesame and safflower oils, both of which contain large amounts of linoleate in triglyceride form, selectively inhibited malignant melanoma growth over normal melanocytes whereas coconut, olive and mineral oils, which contain little or no linoleate as triglyceride, did not. These oils were tested at a range of 10-300 micrograms/ml. We found that of the fatty acids tested, only linoleic acid was selectively inhibitory while palmitic and oleic were not. These fatty acids were tested in the range of 3-100 micrograms/ml. These results suggest that certain vegetable oils rich in linoleic acid, such as the sesame oil, recommended for topical use by Ayurveda, may contain selective antineoplastic properties which are similar to those demonstrated for essential polyunsaturated fatty acids and their metabolites. This suggests that whole vegetable oils may have potential clinical usefulness.

Topics: Antineoplastic Agents; Cell Division; Humans; Linoleic Acid; Linoleic Acids; Medicine, Ayurvedic; Melanocytes; Melanoma; Sesame Oil; Tumor Cells, Cultured

Samples of subcutaneous adipose tissue were taken from 100 melanoma patients and 100 matched controls in Sydney in 1984-1985 and were analyzed for constituent fatty acids. The mean percentage of linoleic acid in the triglycerides of the subcutaneous adipose tissue (PLASAT) of these subjects was substantially higher than that in a similar group examined in 1975-1976. In addition, the percentage of polyunsaturated fatty acids was found to be higher in the melanoma patients than in the controls (p less than 0.01), and there were significantly more controls than patients who had a low PLASAT (p less than 0.01). Relevant literature is quoted and the suggestion is made that increased consumption of dietary polyunsaturates may have a contributory effect in the etiology of melanoma.

Topics: Adipose Tissue; Adult; Aged; Aged, 80 and over; Arachidonic Acid; Arachidonic Acids; Dietary Fats; Fats, Unsaturated; Female; Humans; Linoleic Acid; Linoleic Acids; Male; Melanoma; Middle Aged; Prostaglandins; Triglycerides