alpha-carotene and Liver-Neoplasms

Previous evidence supports that vitamin A decreases the risk of several types of cancer. However, the association between vitamin A and liver cancer is inconclusive.. This systematic review and meta-analysis summarizes the existing literature, discussing the association between vitamin A intake, serum vitamin A, and liver cancer in adult populations.. A systematic literature review was performed by searching the EMBASE, PubMed, Scopus and International Pharmaceutical Abstract databases using terms related to vitamin A (e.g. retinol, α-carotene, β-carotene, and β-cryptoxanthin) and hepatic cancer without applying any time restriction. A meta-analysis was performed using random effect models.. The meta-analysis of five studies showed no association between serum retinol and liver cancer (pooled risk ratio = 1.90 (0.40-9.02); n = 5 studies, I. Current information on the association between vitamin A intake and liver cancer or serum vitamin A and liver cancer are limited. Most studies demonstrated no association between dietary vitamin A and the risk of liver cancer. However, the finding was based on a small number of studies with potential publication bias. Therefore, large observational studies should be conducted to confirm these associations.

Topics: beta Carotene; Beta-Cryptoxanthin; Carotenoids; Humans; Liver Neoplasms; Observational Studies as Topic; Randomized Controlled Trials as Topic; Risk Factors; Vitamin A

Since the incidence of liver cancer is increasing in the world, it is valuable to develop an effective method for its prevention. Various phytochemicals have been shown to suppress liver carcinogenesis in experimental studies. Using these phytochemicals, a clinical trial was conducted. Combination of carotenoids and myo-inositol was found to prevent hepatocellular carcinoma development in patients with chronic viral hepatitis and cirrhosis.

Topics: alpha-Tocopherol; Animals; Anticarcinogenic Agents; beta Carotene; Carcinoma, Hepatocellular; Carotenoids; Cryptoxanthins; Dietary Supplements; Hepatitis, Viral, Human; Humans; Inositol; Kaplan-Meier Estimate; Liver Cirrhosis; Liver Neoplasms; Lycopene; Male; Mice; Mice, Inbred C3H; Tumor Burden; Xanthophylls

In vitro evidence suggests that α-carotene (AC) is an antimetastatic agent against cancer cells, but the mechanistic action is unclear. This study investigated the antimetastatic effect and possible mechanism of AC in comparison with β-carotene (BC) using human hepatocarcinoma SK-Hep-1 cells. Results reveal that treatment with AC (0.5-2.5 μM) for 48 h significantly inhibited invasion, migration, and adhesion of SK-Hep-1 cells in a concentration-dependent manner. These effects of AC were stronger than those of BC at the same concentration (2.5 μM). Mechanistically, AC significantly decreased activities of urokinase plasminogen activator and matrix metalloproteinases (MMP)-2 and -9, but increased protein expression of plasminogen activator inhibitor-1, tissue inhibitor of MMP (TIMP)-1 and -2, and nm23-H1, an antimetastatic protein. AC also attenuated focal adhesion kinase-mediated phosphorylation of mitogen-activated protein kinase family resulting in decreased protein expression of Rho and Rac 1. Overall, these data suggest that AC has potential as an antimetastatic agent.

Topics: Antineoplastic Agents; Carcinoma, Hepatocellular; Carotenoids; Cell Line, Tumor; Cell Movement; Humans; Liver Neoplasms; Matrix Metalloproteinase 2; Mitogen-Activated Protein Kinases; Neoplasm Metastasis; Urokinase-Type Plasminogen Activator

Retinol and its derivatives (retinoids), which have antioxidant activity and promote cell differentiation, may protect against the development of hepatocellular carcinoma (HCC) by controlling hepatocellular differentiation and reducing inflammatory responses.. We examined prospectively the relationship between prediagnostic serum concentrations of retinol, alpha-carotene; beta-carotene; beta-cryptoxanthin; lutein; lycopene; zeaxanthin; alpha-, gamma-, and delta-tocopherols; and selenium and the risk of developing HCC among 213 patients with HCC and 1087 matched control subjects from a cohort of 18,244 men in Shanghai, China, who were monitored from 1986 through 2001. Odds ratios (ORs) and 95% confidence intervals (CIs) for men by quartile of serum concentrations of micronutrients were estimated by using logistic regression with adjustment for cigarette smoking status, alcohol intake, self-reported history of physician-diagnosed hepatitis or liver cirrhosis at recruitment, and seropositivity for hepatitis B surface antigen (HBsAg). All statistical tests were two-sided.. Men with high prediagnostic serum retinol levels had a lower risk of HCC than men in the lowest quartile (Q2 versus Q1, OR = 0.37, 95% CI = 0.22 to 0.61; Q3 versus Q1, OR = 0.30, 95% CI = 0.17 to 0.50; and Q4 versus Q1, OR = 0.13, 95% CI = 0.06 to 0.26; Ptrend < .001). A statistically significant interaction was observed between retinol and HBsAg seropositivity on HCC risk; HBsAg-positive men in the lowest tertile of retinol had a greater than 70-fold higher risk (OR = 72.7, 95% CI = 31.6 to 167.4) of HCC than HBsAg-negative men in the highest tertile of retinol (Pinteraction = .018). No independent effect of serum levels of alpha-carotene; beta-carotene; beta-cryptoxanthin; lutein; lycopene; zeaxanthin; alpha-, gamma-, and delta-tocopherols; or selenium on HCC risk were observed.. High prediagnostic serum level of retinol is associated with a decreased risk of HCC in this population.

Topics: beta Carotene; Carcinoma, Hepatocellular; Carotenoids; Case-Control Studies; China; Cryptoxanthins; Humans; Incidence; Liver Neoplasms; Logistic Models; Lutein; Lycopene; Male; Micronutrients; Middle Aged; Odds Ratio; Prospective Studies; Risk Assessment; Risk Factors; Selenium; Tocopherols; Vitamin A; Xanthophylls; Zeaxanthins

The high incidence of hepatocellular carcinoma (HCC) in cirrhosis, where previous studies have indicated a severe reduction in several antioxidant vitamin factors, prompted us to compare plasma liposoluble vitamins with tocopherol content in healthy and neoplastic liver tissue in humans. This, with a view to a more positive preventive dietary approach, given the conflicting results obtained by liposoluble vitamin dietary supplementation in different malignancies. Eleven patients with cirrhosis, 18 patients affected by cirrhosis with HCC, and 10 patients with liver metastases (LM) from digestive tract adenocarcinomas were compared with controls who had undergone perlaparoscopic cholecistectomy. Plasma alpha- and beta-carotene, retinol and tocopherol, together with liver tocopherol, from both nonmalignant portions and malignant nodules of the same organ, were determined by high-performance liquid chromatography following a well-assessed technique. The results confirm a trend towards a reduction in circulating carotenoids and tocopherol in cirrhosis and in patients affected by cirrhosis with HCC. Tocopherol content in liver tissue is significantly decreased in cirrhosis (0.26 + 0.03 micromol/g prot., mean + SEM, P < .001) and in cirrhotic areas of the HCC group (0.31 + 0.02, P < .002), with respect to its content in liver specimens of healthy controls (0.46 + 0.03) and in healthy areas of the same organ in patients with LM (0.41 + 0.03). Tocopherol concentration is further reduced by 50% in malignant liver nodules of HCC, with respect to surrounding cirrhotic tissue, whereas in metastatic liver nodules from digestive neoplasms the tocopherol content is almost twice that of healthy surrounding areas. This unpredictable tocopherol behavior in liver specimens, of secondary as opposed to primary malignancies of the liver, affords further insight into the conflicting effects of liposoluble vitamins employed in the chemopreventive treatment of different malignant diseases, where hepatic tocopherol concentration show opposite trends: halved in primary HCC and doubled in LM of digestive adenocarcinomas, with respect to healthy controls.

Topics: Aged; beta Carotene; Carcinoma, Hepatocellular; Carotenoids; Female; Humans; Lipids; Liver; Liver Neoplasms; Male; Middle Aged; Vitamin A; Vitamin E

Epidemiological evidence indicates that aflatoxin B1 (AFB1) intake is associated with an increased risk of hepatocellular carcinoma (HCC). The hepatocarcinogenesis is initiated by covalent binding of AFB1 to cellular DNA. To determine whether nutritional factors and hormonal status may influence the binding of AFB1 to hepatic DNA, a cross-sectional study was performed on a total of 42 male asymptomatic hepatitis B surface antigen (HBsAg) carriers and 43 male non-carriers in a cohort study on the multistage development of HCC in Taiwan. The major AFB1-DNA adduct in vivo, AFB1-N7-guanine, was measured by high-performance liquid chromatography in urine. Urinary AFB1-N7-guanine was detectable in 40% of the subjects. HBsAg carriers had a higher detection rate of urinary AFB1-DNA adducts than non-carriers and the difference was statistically significant after multivariate adjustment. After taking into account the total AFB1 urinary metabolite level, chronic HBsAg carrier status, and other potential confounders, plasma levels of cholesterol, alpha-tocopherol, and alpha- and beta-carotene were positively associated with the detection rate of the AFB1-DNA adducts in a dose-dependent manner, whereas plasma lycopene level was inversely related to the presence of the adducts in urine. The association of urinary AFB1-DNA adducts with the plasma levels of cholesterol, alpha-tocopherol, lycopene, and alpha- and beta-carotene was observed at both low and high exposure levels of AFB1. There was a synergistic interaction of plasma alpha-tocopherol with alpha- and beta-carotene on the adduct levels. No association with the adducts was found for plasma levels of retinol and testosterone. This study demonstrated different associations of antioxidant vitamins with AFB1-DNA adduct formation. The data consistent with our previous finding in cultured woodchuck hepatocytes that alpha-tocopherol and beta-carotene enhanced AFB1-DNA adduct formation suggest that prospective investigation of the relationship between plasma micronutrients and risk of AFB1-related HCC is warranted.

Topics: Adult; Aflatoxin B1; Aged; Antioxidants; beta Carotene; Carotenoids; Chronic Disease; DNA; DNA Adducts; Guanine; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Humans; Liver; Liver Neoplasms; Male; Middle Aged; Testosterone; Vitamin E; Vitamins

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