beta-carotene and Neoplasm-Metastasis

Thirty-two typical patients with breast cancer, aged 32-81 years and classified 'high risk' because of tumor spread to the lymph nodes in the axilla, were studied for 18 months following an Adjuvant Nutritional Intervention in Cancer protocol (ANICA protocol). The nutritional protocol was added to the surgical and therapeutic treatment of breast cancer, as required by regulations in Denmark. The added treatment was a combination of nutritional antioxidants (Vitamin C: 2850 mg, Vitamin E: 2500 iu, beta-carotene 32.5 iu, selenium 387 micrograms plus secondary vitamins and minerals), essential fatty acids (1.2 g gamma linolenic acid and 3.5 g n-3 fatty acids) and Coenzyme Q10 (90 mg per day). The ANICA protocol is based on the concept of testing the synergistic effect of those categories of nutritional supplements, including vitamin Q10, previously having shown deficiency and/or therapeutic value as single elements in diverse forms of cancer, as cancer may be synergistically related to diverse biochemical dysfunctions and vitamin deficiencies. Biochemical markers, clinical condition, tumor spread, quality of life parameters and survival were followed during the trial. Compliance was excellent. The main observations were: (1) none of the patients died during the study period. (the expected number was four.) (2) none of the patients showed signs of further distant metastases. (3) quality of life was improved (no weight loss, reduced use of pain killers). (4) six patients showed apparent partial remission.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antioxidants; Ascorbic Acid; beta Carotene; Biomarkers; Breast Neoplasms; Carotenoids; Chemotherapy, Adjuvant; Coenzymes; Combined Modality Therapy; Fatty Acids, Essential; Female; Follow-Up Studies; Humans; Lymphatic Metastasis; Mastectomy; Middle Aged; Neoplasm Metastasis; Quality of Life; Remission Induction; Risk; Selenium; Treatment Outcome; Ubiquinone; Vitamin E

Several studies have demonstrated that single carotenoid, including lycopene, β-carotene, and α-carotene, exhibits antimetastatic effects; however, little is known whether multicarotenoids have similar effects. Herein, we investigated the antimetastatic effect of multicarotenoids at physiological serum levels in Taiwanese (MCT at 1.4 μM) and American (MCA at 1.8 μM) populations using human hepatocarcinoma SK-Hep-1 cells in comparison with single carotenoid, such as lycopene (0.3 or 0.6 μM, respectively), α-carotene (0.1 μM), β-carotene (0.4 μM), lutein (0.4 or 0.5 μM, respectively), and β-cryptoxanthin (0.2 μM). Results reveal that MCA treatment exhibited an additive inhibition on invasion, migration and adhesion at 24 and 48 h of incubation, whereas MCT treatment possessed additive inhibition at 48 h of incubation. The antimetastatic action of MCT and MCA involved additive reduction on activities of matrix metalloproteinase (MMP)-2, -9, and protein expression of Rho and Rac 1 but additive promotion on protein expression of tissue inhibitor of MMP (TIMP)-1 and -2. All of these effects were stronger in MCA than in MCT at 24 and 48 h of incubation. These results demonstrate that multi-carotenoids effectively inhibit metastasis of human hepatocarcinoma SK-Hep-1 cells. More in vivo studies are needed to confirm these findings.

Topics: beta Carotene; Carcinoma, Hepatocellular; Carotenoids; Cell Adhesion; Cell Line, Tumor; Cell Movement; Cryptoxanthins; Humans; Lutein; Lycopene; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Neoplasm Metastasis; rac1 GTP-Binding Protein; rho-Associated Kinases; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2

Lycopene has been shown to inhibit tumor metastasis in vitro, but it is unclear whether lycopene is antimetastatic in vivo. Here, nude mice were orally supplemented 2 times per week for 12 wk with a low or high dose of lycopene [1 or 20 mg/kg body weight (BW)] or with beta-carotene (20 mg/kg BW). Two weeks after the beginning of supplementation, mice were injected once with human hepatoma SK-Hep-1 cells via the tail vein. Plasma levels of matrix metalloproteinase (MMP)-2 and vascular endothelial growth factor (VEGF) increased gradually in tumor-injected mice (tumor controls) following tumor injection but were markedly lowered by lycopene or beta-carotene supplementation. Ten weeks after tumor injection, mice were killed and tumor metastasis was found to be confined to the lungs. Compared with the tumor controls, high-lycopene supplementation lowered the mean number of tumors from 14 +/- 8 to 3 +/- 5 (P < 0.05) and decreased tumor cross-sectional areas by 62% (P < 0.05). High-lycopene supplementation also decreased the positive rate of proliferating cellular nuclear antigen (PCNA), the level of VEGF, and protein expressions of PCNA, MMP-9, and VEGF in lung tissues. However, high-lycopene increased the protein expression of nm23-H1 (an antimetastatic gene) by 133% (P < 0.001). For most variables measured, effects of lycopene were dose dependent and the effect of beta-carotene was between those of high-dose and low-dose lycopene. These results show that lycopene supplementation reduces experimental tumor metastasis in vivo and suggest that such an action is associated with attenuation of tumor invasion, proliferation, and angiogenesis.

Topics: Animals; beta Carotene; Body Weight; Carcinoma, Hepatocellular; Carotenoids; Cell Line, Tumor; Diet; Dietary Supplements; Gene Expression Regulation; Humans; Interleukin-12; Lung Neoplasms; Lycopene; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Mice, Nude; Neoplasm Metastasis; Neoplasms, Experimental; NM23 Nucleoside Diphosphate Kinases; Proliferating Cell Nuclear Antigen; Vascular Endothelial Growth Factor A

Greater adult height, which reflects a combination of early nutrition, exposure to androgens, growth hormones, and other factors during growth and development, as well as heredity, has been associated with increased prostate cancer risk in several observational studies, but findings have been inconsistent. We examined this relationship in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. At baseline, 29,119 Finnish male smokers 50 to 69 years old had height and weight measured by trained personnel, provided information on demographic, smoking, medical, and other characteristics, and completed an extensive diet history questionnaire. A total of 1,346 incident prostate cancer cases were identified during a follow-up period of up to 17.4 years (median, 14.1 years). In age-adjusted Cox proportional hazards models, the hazard ratios and 95% confidence intervals for prostate cancer according to increasing quintiles of height [178 cm] were 1.00 (reference), 1.11 (0.93-1.32), 1.11 (0.95-1.31), 1.30 (1.01-1.55), and 1.14 (0.96-1.35); P(trend) = 0.04. In analyses stratified by disease stage (available for 916 cases), a strong dose-response relationship was observed between greater height and advanced, but not earlier-stage, disease [tumor-node-metastasis stage III-IV, hazard ratio and 95% confidence interval for increasing quintiles of height: 1.77 (1.18-2.65), 1.82 (1.25-2.65), 1.93 (1.29-2.90), and 2.02 (1.37-2.97); P(trend) = 0.0008, P(interaction) = 0.002]. Our study provides additional evidence that increased height is a risk factor for prostate cancer and suggests that taller men are particularly susceptible to advanced disease.

Topics: Aged; alpha-Tocopherol; beta Carotene; Body Height; Cohort Studies; Follow-Up Studies; Growth Hormone; Humans; Male; Middle Aged; Neoplasm Metastasis; Proportional Hazards Models; Prospective Studies; Prostatic Neoplasms; Risk Factors

Biological therapies are new additions to breast cancer treatment. Among biological compounds, beta-carotene has been reported to have immune modulatory effects, in particular, enhancement of natural killer cell activity and tumor necrosis factor-alpha production by macrophages. The objective of this study was to investigate the effect of palm carotene supplementation on the tumorigenicity of MCF-7 human breast cancer cells injected into athymic nude mice and to explore the mechanism by which palm carotenes suppress tumorigenesis. Forty-eight 4-wk-old mice were injected with 1 x 10(6) MCF-7 cells into their mammary fat pad. The experimental group was supplemented with palm carotene whereas the control group was not. Significant differences were observed in tumor incidence (P< 0.001) and tumor surface area and metastasis to lung (P< 0.005) between the two groups. Natural killer (NK) cells and B-lymphocytes in the peripheral blood of carotene-supplemented mice were significantly increased (P < 0.05 and P < 0.001, respectively) compared with controls. These results suggest that palm oil carotene is able to modulate the immune system by increasing peripheral blood NK cells and B-lymphocytes and suppress the growth of MCF-7 human breast cancer cells.

Topics: Adipose Tissue; Animals; beta Carotene; Breast Neoplasms; Chromatography, High Pressure Liquid; Humans; Liver; Mice; Mice, Nude; Neoplasm Metastasis; Neoplasm Transplantation; Palm Oil; Plant Oils

We investigated the effects of astaxanthin on the antitumor effector activity of natural killer (NK) cells suppressed by stress in mice in order to define the immunological significance of astaxanthin (ASX) when combined with restraint stress treatment. When the mice were treated with restraint stress alone, the total number of spleen cells, and the level NK cell activity per spleen were reduced to a nadir on day 3. The stress also caused a significant increase in the lipid peroxidation of liver tissue. ASX (100 mg/kg/day, p.o., 4 days) improved the immunological dysfunction induced by restraint stress. On the other hand, metastatic nodules were observed in the livers of syngenic DBA/2 mice on day 12 after inoculation of P815 mastocytoma cells. Hepatic metastasis was promoted further by restraint stress when applied on day 3 before the inoculation of P815. Daily oral administration of ASX (1 mg/kg/day, p.o., 14 days) markedly attenuated the promotion of hepatic metastasis induced by restraint stress. These results suggested that astaxanthin improves antitumor immune responses by inhibiting of lipid peroxidation induced by stress.

Topics: Animals; Antineoplastic Agents, Phytogenic; Antioxidants; beta Carotene; Cells, Cultured; Female; Immunosuppressive Agents; Killer Cells, Natural; Lipid Peroxidation; Liver; Liver Neoplasms; Mast-Cell Sarcoma; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Neoplasm Metastasis; Neoplasm Transplantation; Restraint, Physical; Stress, Psychological; Thiobarbituric Acid Reactive Substances; Tissue Distribution; Tumor Cells, Cultured; Xanthophylls

We conducted a follow-up study of 380 incident cases of cancer of the oral cavity, pharynx, or larynx, who had been included in a previous case-control study. Information pertaining to potential risk factors, clinical characteristics, and evolution of the tumor (vital status, metastases, and second primary tumors) was obtained. From a multivariate proportional hazard model including terms for risk factors and clinical variables, the incidence of metachronous second primary tumors occurring in the head and neck was positively associated with employment as a farmer as opposed to white collar (hazard ratio [HR] = 3.3) and with tobacco smoking before first tumor diagnosis (HR = 4.3 for heavy versus never or very light smoker). The risk of second primary tumor decreased with increasing dietary "beta-carotene" intake (HR = 0.4 for high versus low intake in tertiles). Less differentiated first primary tumors were followed more frequently by second tumors as compared to grade 1 tumors. The incidence of metastases was not associated with etiological factors of the first tumor, but with stage.

Topics: Adult; Aged; Aged, 80 and over; Alcohol Drinking; Antineoplastic Agents; beta Carotene; Carotenoids; Case-Control Studies; Cohort Studies; Female; Follow-Up Studies; Humans; Laryngeal Neoplasms; Male; Middle Aged; Mouth Neoplasms; Neoplasm Metastasis; Neoplasms, Second Primary; Occupations; Pharyngeal Neoplasms; Risk Factors; Smoking