alpha-carotene and Lung-Neoplasms

beta-Carotene and Retinol Efficacy Trial is a nationwide chemoprevention trial that recruited 18,314 high-risk individuals to test the effect of supplemental beta-carotene and retinol on lung cancer incidence. In this report, we conducted a prospective nested case-control study of the association between serum carotenoids, retinoids, and tocopherols on both lung and prostate cancer incidence. Prerandomization serum samples were selected from 278 lung cancer cases and 205 prostate cancer cases, and 483 controls matched by high-risk population, study center location, age, sex (lung cancer only), smoking status, and year of randomization. Carotenoids, retinoids, and tocopherols were analyzed by high-performance liquid chromatography. Endpoints were confirmed by pathology review (lung cancer) or review of the pathology report (prostate cancer). In the control-only population, there was a significant association between tobacco use and serum micronutrient concentration. Current smokers compared with former smokers had lower mean levels of all of the micronutrients tested with zeaxanthin, beta-cryptoxanthin, alpha-carotene, alpha-tocopherol, retinol, and retinyl palmitate reaching statistical significance at P = 0.05. In the overall population, the mean serum concentrations of all of the micronutrients except gamma-tocopherol were lower for lung cancer cases than controls. Statistically significant trends across quartiles were observed in lutein (P = 0.02), zeaxanthin (P = 0.02), and alpha-tocopherol (P = 0.03). The carotenoid findings in the overall population were because of the strong inverse association between serum micronutrients and lung cancer in females. Statistically significant odds ratios (ORs) comparing 4(th) to 1st quartiles in the female population were seen in lutein [OR, 0.31; confidence interval (CI), 0.13-0.75], zeaxanthin (OR, 0.31; CI, 0.12-0.77), and beta-cryptoxanthin (OR, 0.34; CI, 0.14-0.81). For prostate cancer, mean serum concentrations were lower in cases for all of the nutrients except alpha-carotene. Only for alpha-tocopherol (P(trend) = 0.04) were the findings statistically significant. There was no statistically significant association between serum carotenoids and prostate cancer. Our findings provide additional support for the association between physiological levels of dietary micronutrients and cancer incidence.

Topics: Aged; alpha-Tocopherol; Antioxidants; beta Carotene; Biomarkers, Tumor; Carotenoids; Case-Control Studies; Double-Blind Method; Female; gamma-Tocopherol; Humans; Lung Neoplasms; Male; Micronutrients; Middle Aged; Prospective Studies; Prostatic Neoplasms; Risk Factors; Smoking; Statistics as Topic; Treatment Outcome; Vitamin A

This study aimed to investigate the anti-metastatic activity of α-carotene (AC) in Lewis lung carcinoma (LLC) and in combination with taxol in LLC-xenografted C57BL/6 mice. Cell culture studies reveal that AC significantly inhibited invasion, migration and activities of matrix metalloproteinase (MMP)-2, -9 and urokinase plasminogen activator but increased protein expression of tissue inhibitor of MMP (TIMP)-1, -2 and plasminogen activator inhibitor (PAI)-1. These effects of AC are similar to those of β-carotene at the same concentration (2.5 μM). AC (2.5 μM) also significantly inhibited integrin β1-mediated phosphorylation of focal adhesion kinase (FAK) which then decreased the phosphorylation of MAPK family. Findings from the animal model reveal that AC treatment (5m g/kg) alone significantly decreased lung metastasis without affecting primary tumor growth, whereas taxol treatment (6 mg/kg) alone exhibited significant inhibition on both actions, as compared to tumor control group. AC treatment alone significantly decreased protein expression of integrin β1 but increased protein expression of TIMP-1 and PAI-1 without affecting protein expression of TIMP-2 and phosphorylation of FAK in lung tissues, whereas taxol treatment alone significantly increased protein expression of TIMP-1, PAI-1 and TIMP-2 but decreased protein expression of integrin β1 and phosphorylation of FAK. The combined treatment produced stronger actions on lung metastasis and lung tissues protein expression of TIMP-1, TIMP-2 and PAI-1. Overall, we demonstrate that AC effectively inhibits LLC metastasis and suppresses lung metastasis in combination with taxol in LLC-bearing mice, suggesting that AC could be used as an anti-metastatic agent or as an adjuvant for anti-cancer drugs.

Topics: Animals; Antineoplastic Agents, Phytogenic; Carcinoma, Lewis Lung; Carotenoids; Focal Adhesion Kinase 1; Lung Neoplasms; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Mice, Inbred C57BL; Paclitaxel; Plasminogen Activator Inhibitor 1; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2; Urokinase-Type Plasminogen Activator; Xenograft Model Antitumor Assays

Lung cancer is one of the most common cancers worldwide and is the leading cause of cancer-induced death in the USA. Although much attention has been focused on the anti-carcinogenic effect of consuming carotenoid-containing food or supplements, the results have been inconsistent. We investigated whether serum carotenoid levels were associated with the mortality risk of lung cancer in US adults using data from a nationally representative sample. The data were obtained from the Third Nutrition and Health Examination Survey (NHANES III) database and the NHANES III Linked Mortality File. A total of 10,382 participants aged over 20,years with available serum carotenoid levels and no other missing information on questionnaires and biomarkers at baseline (NHANES III) were included in the present study. Of the 10,382 participants, 161 subjects died due to lung cancer. We found that high serum levels of alpha-carotene and beta-cryptoxanthin at baseline were significantly associated with a lower risk of lung cancer death. When we stratified the risk by current smoking status, the risk of death of current smokers was significantly decreased to 46% (95% confidence interval, 31-94%) for alpha-carotene and 61% (95% confidence interval, 19-80%) for beta-cryptoxanthin. By contrast, no association was observed among never/former smokers at baseline. High serum levels of alpha-carotene and beta-cryptoxanthin are associated with a lower risk of lung cancer death in US adults.

Topics: Adult; Biomarkers, Tumor; Carotenoids; Cohort Studies; Cryptoxanthins; Female; Humans; Lung Neoplasms; Male; Middle Aged; Prospective Studies; Risk; Risk Factors; Smoking; Surveys and Questionnaires; United States; Xanthophylls

To investigate whether high serum levels of carotenoids, tocopherols, and folic acid decrease risk of lung cancer in Japanese, we conducted a case-control study nested in the Japan Collaborative Cohort (JACC) Study. A total of 39,140 subjects provided serum samples at baseline between 1988 and 1990. We identified 147 cases (113 males and 34 females) of death from lung cancer during an 8-year follow-up. Of the subjects who survived to the end of this follow-up, 311 controls (237 males and 74 females) were selected, matched to each case of lung cancer death for gender, age and participating institution. We measured serum levels of antioxidants in cases of lung cancer death and controls. Odds ratios (ORs) for lung cancer death were estimated using conditional logistic models. The risk of lung cancer death for the highest quartile of serum alpha-carotene, beta-carotene, lycopene, beta-cryptoxanthin, and canthaxanthin was significantly or marginally significantly lower than for the lowest quartile: the ORs, adjusted for smoking and other covariates, were 0.35 (95% confidence interval (CI), 0.14-0.88), 0.21 (0.08-0.58), 0.46 (0.21-1.04), 0.44 (0.17-1.16) and 0.37 (0.15-0.91), respectively. The ORs for the highest serum levels of zeaxanthin/lutein and folic acid tended to be low, but the differences were not statistically significant. Serum total cholesterol was also inversely related to risk of lung cancer death: the OR for the highest vs. the lowest quartile was 0.39 (95% CI, 0.19-0.79). Higher serum levels of carotenoids such as alpha- and beta-carotenes may play a role in preventing death from lung cancer among Japanese.

Topics: Adult; Aged; Alcohol Drinking; Anticarcinogenic Agents; Antioxidants; beta Carotene; Body Mass Index; Canthaxanthin; Carotenoids; Case-Control Studies; Cholesterol; Cohort Studies; Cryptoxanthins; Feeding Behavior; Female; Folic Acid; Follow-Up Studies; Humans; Japan; Life Style; Lung Neoplasms; Lutein; Lycopene; Male; Middle Aged; Odds Ratio; Smoking; Tocopherols; Vitamin A; Xanthophylls

Topics: Carotenoids; Edible Grain; Feeding Behavior; Folic Acid; Fruit; Humans; Lung Neoplasms; Lutein; Lycopene; Nutrition Policy; Smoking; Vegetables

Carotenoids may reduce lung carcinogenesis because of their antioxidant properties; however, few studies have examined the relation between intakes of individual carotenoids and lung cancer risk.. The aim of this study was to examine the relation between lung cancer risk and intakes of alpha-carotene, beta-carotene, lutein, lycopene, and beta-cryptoxanthin in 2 large cohorts.. During a 10-y follow-up period, 275 new cases of lung cancer were diagnosed in 46924 men; during a 12-y follow-up period, 519 new cases were diagnosed in 77283 women. Carotenoid intakes were derived from the reported consumption of fruit and vegetables on food-frequency questionnaires administered at baseline and during follow-up. The data were analyzed separately for each cohort and the results were pooled to compute overall relative risks (RRs).. In the pooled analyses, alpha-carotene and lycopene intakes were significantly associated with a lower risk of lung cancer; the association with beta-carotene, lutein, and beta-cryptoxanthin intakes were inverse but not significant. Lung cancer risk was significantly lower in subjects who consumed a diet high in a variety of carotenoids (RR: 0.68; 95% CI: 0.49, 0.94 for highest compared with lowest total carotenoid score category). Inverse associations were strongest after a 4-8-y lag between dietary assessment and date of diagnosis. In subjects who never smoked, a 63% lower incidence of lung cancer was observed for the top compared with the bottom quintile of alpha-carotene intake (RR: 0.37; 95% CI: 0.18, 0.77).. Data from 2 cohort studies suggest that several carotenoids may reduce the risk of lung cancer.

Topics: Adult; Aged; beta Carotene; Carotenoids; Cohort Studies; Cryptoxanthins; Eating; Female; Humans; Linear Models; Lung Neoplasms; Lutein; Lycopene; Male; Middle Aged; Prospective Studies; Regression Analysis; Risk Factors; Smoking; Surveys and Questionnaires; Xanthophylls

Lung cancers occur more commonly in the upper lobes than in the lower lobes, but its pathophysiologic basis is not well understood. Because numerous studies have reported a consistent inverse relationship between lung cancer risk and intake of certain vegetables and fruits, we hypothesized that the balance between diet-derived protective substances delivered via the circulation and cigarette-derived carcinogenic substances delivered via the airways would be less favorable in the upper lobes compared with the lower lobes, hence accounting for the upper lobe predominance of tumors among smokers. Thus, we examined the association between diet and tumor location in 328 patients with lung cancer. The ratio of upper to lower lobe tumors was 2.5:1.0. In univariate analysis, age, height, weight, sex, race, family history of cancer, education level, tumor histology, calories consumed per day, and intake of animal fat did not differ significantly between patients with upper versus lower lobe tumors. Predictors of tumor location in univariate analysis were family history of lung cancer; smoking history; history of asbestos exposure; and intakes of yellow-orange vegetables, alpha-carotene, beta-carotene, and vitamins A, C, and E. In multivariable logistic regression analysis, the independent predictors of upper lobe tumor location were family history of lung cancer (p = 0.03), history of asbestos exposure (p = 0.02), less intake of yellow-orange vegetables (p < 0.04), and less intake of vitamin E (p = 0.05). Our results show a strong inverse association between upper lobe location of lung cancer and intake of yellow-orange vegetables and vitamin E.

Topics: Administration, Inhalation; Age Factors; Aged; Analysis of Variance; Anticarcinogenic Agents; Antioxidants; Asbestos; Ascorbic Acid; beta Carotene; Carcinogens; Carotenoids; Diet; Dietary Fats; Educational Status; Energy Intake; Female; Forecasting; Fruit; Humans; Logistic Models; Lung; Lung Neoplasms; Male; Racial Groups; Risk Factors; Sex Factors; Smoking; Vegetables; Vitamin A; Vitamin E

Most studies concerning a possible protective role of carotenoids against cancer focus on serum carotenoid levels. We have used Raman microspectroscopy to study the intracellular amounts of carotenoids in lymphocytes of lung cancer patients and of healthy individuals. Our results indicate a significant decrease of carotenoids in lung carcinoma patients compared with healthy individuals, particularly in adenocarcinoma patients. Carotenoid supplementation raised the serum concentration in 2 lung cancer patients up to normal levels, whereas intracellular content remained significantly lower. This indicates that carotenoid uptake by lymphocytes is not only dependent on serum carotenoid concentration. Our findings indicate that Raman microspectroscopy, a recently developed technique to measure intracellular levels of drugs, is also well suited to obtain quantitative data on carotenoid amounts inside cells.

Topics: Adenocarcinoma; Adult; Age Factors; Aged; beta Carotene; Carotenoids; Chromatography, High Pressure Liquid; Cryptoxanthins; Food, Fortified; Humans; Lung Neoplasms; Lycopene; Lymphocytes; Reference Values; Spectrum Analysis, Raman; Xanthophylls

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; beta Carotene; Carotenoids; Case-Control Studies; Confounding Factors, Epidemiologic; Diet; Fruit; Humans; Lung Neoplasms; Male; Middle Aged; Risk; Smoking; Surveys and Questionnaires; Tracheal Neoplasms; Vegetables

The antiproliferative properties of lycopene, the major tomato carotenoid, were compared with those of alpha- and beta-carotene. Lycopene, delivered in cell culture medium from stock solutions in tetrahydrofuran, strongly inhibited proliferation of endometrial (Ishikawa), mammary (MCF-7), and lung (NCI-H226) human cancer cells with half-maximal inhibitory concentration of 1-2 microM; alpha- and beta-carotene were far less effective inhibitors. For example, in Ishikawa cells, a 4-fold higher concentration of alpha-carotene or a 10-fold higher concentration of beta-carotene was needed for the same order of growth suppression. The inhibitory effect of lycopene was detected after 24 hours of incubation, and it was maintained for at least three days. In contrast to cancer cells, human fibroblasts were less sensitive to lycopene, and the cells gradually escaped growth inhibition over time. In addition to its inhibitory effect on basal endometrial cancer cell proliferation, lycopene also suppressed insulin-like growth factor-I-stimulated growth. Insulin-like growth factors are major autocrine/paracrine regulators of mammary and endometrial cancer cell growth. Therefore, lycopene interference in this major autocrine/paracrine system may open new avenues for research on the role of lycopene in the regulation of endometrial cancer and other tumors.

Topics: Anticarcinogenic Agents; beta Carotene; Breast Neoplasms; Carotenoids; Cell Division; DNA; Dose-Response Relationship, Drug; Endometrial Neoplasms; Female; Humans; Insulin-Like Growth Factor I; Lung Neoplasms; Lycopene; Tumor Cells, Cultured

Topics: Anticarcinogenic Agents; beta Carotene; Carcinoma, Small Cell; Carotenoids; Cell Division; Cell Line; Gene Expression; Genes, myc; Humans; Kinetics; Lung Neoplasms; RNA, Messenger; Tumor Cells, Cultured

Although beta-carotene has been considered to be a key cancer preventive agent in green and yellow vegetables, other types of carotenoids, such as alpha-carotene, may also contribute to anticarcinogenic action, since these carotenoids usually coexist with beta-carotene and are detectable in human blood and tissues. In this study, we compared the inhibitory effect of natural alpha-carotene, obtained from palm oil, with that of beta-carotene on spontaneous liver carcinogenesis in C3H/He male mice. The mean number of hepatomas per mouse was significantly decreased by alpha-carotene supplementation (per os administration in drinking water at a concentration of 0.05%, ad libitum) as compared with that in the control group (P < 0.001, Student's t test). On the other hand, beta-carotene, at the same dose as alpha-carotene, did not show any such significant difference from the control group. Furthermore, we also compared the antitumor-promoting activity of alpha-carotene with that of beta-carotene against two-stage mouse lung carcinogenesis (initiator, 4-nitroquinoline 1-oxide; promoter, glycerol). alpha-Carotene, but not beta-carotene, reduced the number of lung tumors per mouse to about 30% of that in the control group (P < 0.001, Student's t test). The higher potency of the antitumor-promoting action of alpha-carotene compared to beta-carotene was confirmed in other experimental systems; e.g., alpha-carotene was also found to have a stronger effect than beta-carotene in suppressing the promoting activity of 12-O-tetradecanoylphorbol-13-acetate on skin carcinogenesis in 7,12-dimethylbenz[a]anthracene-initiated mice. These results suggest that not only beta-carotene, but also other types of carotenoids, such as alpha-carotene, may play an important role in cancer prevention.

Topics: 4-Nitroquinoline-1-oxide; 9,10-Dimethyl-1,2-benzanthracene; Administration, Oral; Animals; beta Carotene; Carotenoids; Drug Screening Assays, Antitumor; Humans; Liver Neoplasms; Lung Neoplasms; Male; Mice; Mice, Inbred C3H; Ornithine Decarboxylase; Papilloma; Skin Neoplasms; Specific Pathogen-Free Organisms; Tetradecanoylphorbol Acetate