beta-carotene and Melanoma

Mounting evidence from experimental and animal studies suggests that vitamin A may have a protective effect on melanoma, but the findings on the association of vitamin A intake with risk of melanoma have been inconsistently reported in epidemiologic studies. We attempted to elucidate the association by performing a meta-analysis.. Eligible studies were identified by searching PubMed and EMBASE databases, as well as by reviewing the references of retrieved publications. Summary odds ratios (OR) with corresponding 95% confidence interval (CI) were computed with a random-effects model. Study-specific ORs and 95% CIs for the highest vs. lowest categories of vitamin A intake were pooled.. A total of 8 case-control studies and 2 prospective studies comprising 3,328 melanoma cases and 233,295 non-case subjects were included. The summary OR for the highest compared with the lowest intake of total vitamin A, retinol and beta-carotene was 0.86 (95% CI = 0.59-1.25), 0.80 (95% CI = 0.69-0.92) and 0.87 (95%CI = 0.62-1.20), respectively. Significant heterogeneity was observed among studies on vitamin A and beta-carotene intake, but not among studies on retinol intake. Subgroup and sensitivity analyses confirmed these findings. There was no indication of publication bias.. Findings from this meta-analysis suggest that intake of retinol, rather than of total vitamin A or beta-carotene, is significantly associated with reduced risk of melanoma.

Topics: beta Carotene; Case-Control Studies; Humans; Melanoma; Prospective Studies; Skin; Skin Neoplasms; Vitamin A; Vitamins

Photodamage is known to occur in skin with exposure to sunlight, specifically ultraviolet (UV) radiation. Such damage includes inflammation, oxidative stress, breakdown of the extracellular matrix, and development of cancer in the skin. Sun exposure is considered to be one of the most important risk factors for both nonmelanoma and melanoma skin cancers. Many phytonutrients have shown promise as photoprotectants in clinical, animal and cell culture studies. In part, the actions of these phytonutrients are thought to be through their actions as antioxidants. In regard to skin health, phytonutrients of interest include vitamin E, certain flavonoids, and the carotenoids, β-carotene, lycopene and lutein.

Topics: Animals; Antioxidants; beta Carotene; Carotenoids; Flavonoids; Humans; Lutein; Lycopene; Melanoma; Mice; Oxidative Stress; Rats; Skin Neoplasms; Sunlight; Ultraviolet Rays; Vitamin E

Topics: Animals; Anticarcinogenic Agents; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Case-Control Studies; Cell Transformation, Neoplastic; Diet; Free Radicals; Guinea Pigs; Humans; Incidence; Lung Neoplasms; Melanoma; Mice; Mice, Hairless; Models, Chemical; Neoplasms; Neoplasms, Radiation-Induced; Oxygen; Partial Pressure; Prospective Studies; Reactive Oxygen Species; Retrospective Studies; Selenium; Singlet Oxygen; Skin Neoplasms; Smoking; Structure-Activity Relationship; Ultraviolet Rays; Vegetables; Vitamin E

Topics: Aging; Animals; Antioxidants; beta Carotene; Carcinogens; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Carotenoids; DNA; Female; Geography; Humans; Male; Melanocytes; Melanoma; Neoplasms, Radiation-Induced; Pyrimidine Dimers; Sex Factors; Skin Neoplasms; Ultraviolet Rays; Vitamin A

The Physicians' Health Study was a randomized, double-blind, placebo-controlled trial using a 2x2 factorial design including supplementation with beta-carotene (50 mg every other day) in the primary prevention of cancer among 22,071 U.S. male physicians ages 40-84 years at randomization. Before randomization, the authors collected baseline blood specimens to determine whether any benefit was greater among or confined to those with low baseline levels of beta-carotene.. Baseline blood samples were collected from 14,916 participants. These samples were assayed, according to a nested case-control design, from 1439 men subsequently diagnosed with cancer over 12 years of follow-up (631 with prostate carcinoma) and 2204 controls matched by age and smoking habits.. Men in the lowest quartile for plasma beta-carotene at baseline had a marginally significant (P = 0.07) increased risk of cancer compared with those in the highest quartile (relative risk [RR] = 1.30, 95% confidence interval [CI], 0.98-1.74). Men in the lowest quartile assigned at random to beta-carotene supplementation had a possible but nonsignificant decrease in overall cancer risk (RR = 0.83, 95% CI, 0.63-1.09) compared with those assigned to placebo. This was primarily due to a significant reduction in the risk of prostate carcinoma (RR = 0.68, 95% CI, 0. 46-0.99) in this group. After the first 2 years of follow-up were excluded, the results were virtually unchanged.. These prespecified subgroup analyses appeared to support the idea that beta-carotene supplementation may reduce risk of prostate carcinoma among those with low baseline levels. Further follow-up of this population will help determine whether these findings are valid.

Topics: Adult; Aged; Aged, 80 and over; beta Carotene; Case-Control Studies; Colonic Neoplasms; Dietary Supplements; Double-Blind Method; Epidemiologic Studies; Follow-Up Studies; Humans; Lung Neoplasms; Lymphoma; Male; Melanoma; Middle Aged; Prostatic Neoplasms; Risk; Smoking

Two series of examinations were carried out in two voluntary test groups for the purpose of elucidating the correlation between ultraviolet light load and oxidative stress as well as the way it is influenced by nutritive radical scavengers. After a 6 to 7-hour impact of sunshine on the whole body (sunbathing beach) at n = 8 a continuous progredient increase of thiobarbituric acid reactive substances could be identified in the serum (from 5.56 +/- 0.98 to 8.91 +/- 0.99 mumol/l, p < 0.001), which after new exposure to sunshine reached 11.3 +/- 2.4 mumol/l. Likewise, a 15-minute exposure to ultraviolet light at n = 24 induced increases of TBRS concentrations lasting from 1-2 days. After 14-day supplementation with beta-carotene (n = 6), D-alpha-tocopherol (n = 6), selenium (n = 6), and ginkgo biloba extract (n = 6) the extent of the oxidative stress could be inhibited during a second exposure to ultraviolet light up to the following efficiency: Se > Ginkgo > beta-carotene > vitamin E. The clastogenous effect of sunshine and ultraviolet light must be regarded as a factor for initiating and promoting cancerogenesis in the total organism. Concerning the aetiopathogenesis of malignant melanoma the paramagnetic properties of free radicals with their nonenergetic effects of the magnetic field have to be considered more carefully in scientific examinations.

Topics: Adult; beta Carotene; Carotenoids; DNA Damage; Female; Free Radical Scavengers; Ginkgo biloba; Humans; Male; Malondialdehyde; Melanoma; Neoplasms, Radiation-Induced; Plant Extracts; Selenium; Skin Neoplasms; Sunlight; Ultraviolet Rays; Vitamin E

Raman spectroscopy is an emerging dermatological technique with the potential to discriminate biochemically between cell types in a label-free and non-invasive manner. Here, we use live single-cell Raman spectroscopy and principal component analysis (PCA) to fingerprint mouse melanoblasts, melanocytes, keratinocytes and melanoma cells. We show the differences in their spectra are attributable to biomarkers in the melanin biosynthesis pathway and that melanoma cells are a heterogeneous population that sit on a trajectory between undifferentiated melanoblasts and differentiated melanocytes. We demonstrate the utility of Raman spectroscopy as a highly sensitive tool to probe the melanin biosynthesis pathway and its immediate response to ultraviolet (UV) irradiation revealing previously undescribed opposing responses to UVA and UVB irradiation in melanocytes. Finally, we identify melanocyte-specific accumulation of β-carotene correlated with a stabilisation of the UVR response in lipids and proteins consistent with a β-carotene-mediated photoprotective mechanism. In summary, our data show that Raman spectroscopy can be used to determine the differentiation status of cells of the melanocyte lineage and describe the immediate and temporal biochemical changes associated with UV exposure which differ depending on cell type, differentiation status and competence to synthesise melanin. Our work uniquely applies Raman spectroscopy to discriminate between cell types by biological function and differentiation status while they are growing in culture. In doing so, we demonstrate for the first time its utility as a tool with which to probe the melanin biosynthesis pathway.

Topics: Animals; beta Carotene; Cells, Cultured; Keratinocytes; Lipids; Melanins; Melanocytes; Melanoma; Mice; Spectrum Analysis, Raman; Ultraviolet Rays

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

Our interest continues in discovering phytocomplexes from medicinal plants with phototoxic activity against human melanoma cells; thus the aim of the present study was to assess antioxidant, anti-inflammatory and phototoxic activity of Hypericum perforatum L. subsp. perforatum, and relate these properties to the plant's chemical composition.. Components of H. perforatum subsp. perforatum were extracted by hydroalcoholic solution and chemical profiles of preparations (HyTE-3) performed by HPTLC. Linoleic acid peroxidation and DPPH tests were used to assess antioxidant activity, while MTT assay allowed evaluation of anti-proliferative activity with respect to A375 human melanoma cells after irradiation with UVA dose, 1.8 J/cm(2) . Inhibition of nitric oxide production of macrophages was also investigated.. HyTE-3 indicated better antioxidant activity with β-carotene bleaching test in comparison to DPPH assay (IC50 = 0.89 μg/ml); significant phototoxicity in A375 cells at 78 μg/ml concentration resulted in cell destruction of 50%. HyTE-3 caused significant dose-related inhibition of nitric oxide production in murine monocytic macrophage cell line RAW 264.7 with IC50 value of 342 μg/ml.. The H. perforatum subsp. perforatum-derived product was able to suppress proliferation of human malignant melanoma A375 cells; extract together with UVA irradiation enhanced phototoxicity. This biological activity of antioxidant effects was combined with inhibition of nitric oxide production.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents, Phytogenic; beta Carotene; Cell Line, Tumor; Cell Proliferation; Free Radical Scavengers; Free Radicals; Humans; Hypericum; Inhibitory Concentration 50; Macrophages; Melanoma; Mice; Nitric Oxide; Phenols; Photosensitizing Agents; Plant Components, Aerial; Plant Extracts; Ultraviolet Rays

Beta-carotene is a ubiquitous compound rich in foods. However, there are conflicting reports regarding its role in carcinogenesis. We performed a microarray expression analysis in normal [human umbilical vein endothelial cells (HUVECs)] and neoplastic (melanoma A375 and myelomonocytic leukemia U937) actively proliferating cells and found evidence that beta-carotene stimulated vital cellular functions in the former and suppressed them in the latter. These differential effects correlated with the expression of the proapoptotic BCL2-associated X protein (BAX), which was downregulated in HUVECs and upregulated in the two neoplastic cell lines. The quantitative expression analysis using real-time polymerase chain reaction largely confirmed the inhibition of B-cell CLL/lymphoma 2 (BCL2) pathway-mediated apoptosis in HUVECs and its activation in melanoma and leukemic cells. The assays for apoptosis, detecting DNA breaks and caspase activation, showed consistent proapoptotic and antiapoptotic effects in U937 and HUVEC lines, respectively. However, beta-carotene-induced expression changes of BAX and other BCL2 pathway genes did not lead to the predicted induction of apoptosis in the A375 cells.

Topics: Antioxidants; Apoptosis; bcl-2-Associated X Protein; beta Carotene; Cells, Cultured; DNA Damage; Drug Synergism; Endothelial Cells; Gene Expression; Gene Expression Profiling; Humans; In Situ Nick-End Labeling; In Vitro Techniques; Leukemia, Myelomonocytic, Acute; Melanoma; Models, Biological; Protein Array Analysis; Proto-Oncogene Proteins c-bcl-2; Reference Values; Reverse Transcriptase Polymerase Chain Reaction; Tumor Cells, Cultured; Umbilical Veins

In this study, we examined possible mechanisms of caspase activation during carotenoid-induced apoptosis in tumor cells. We found that beta-Carotene induces apoptosis by the activation of caspase-3 in human leukemia (HL-60), colon adenocarcinoma (HT-29) as well as melanoma (SK-MEL-2) cell lines. This activation is dose dependent and follows that of caspase-8 and caspase-9. Although caspase-8 cleavage is an early event, reaching its maximum activation at 3 h, caspase-9 reaches its maximum activation only at 6 h. The addition of IETD-CHO, a caspase-8-specific inhibitor, completely prevents beta-Carotene-induced apoptosis, whereas only a partial prevention was observed in the presence of LEHD-CHO, a caspase-9-specific inhibitor. beta-Carotene activates caspase-9 via cytochrome c release from mitochondria and loss of mitochondrial membrane potential (Dym). Concomitantly, a dose-dependent decrease in the antiapoptotic protein Bcl-2 and a dose-dependent increase in the cleaved form of BID (t-BID) are observed. Moreover, NF-kB activation is involved in beta-Carotene-induced caspase cascade. These results support a pharmacological role for beta-Carotene as a candidate antitumor agent and show a possible sequence of molecular events by which this molecule may induce apoptosis in tumor cells.

Topics: Adenocarcinoma; Apoptosis; beta Carotene; BH3 Interacting Domain Death Agonist Protein; Carrier Proteins; Caspase 3; Caspase 8; Caspase 9; Caspases; Colonic Neoplasms; Cytochromes c; Enzyme Activation; Enzyme Inhibitors; HL-60 Cells; Humans; Melanoma; Membrane Potentials; Mitochondria; Neoplasms; NF-kappa B; Proto-Oncogene Proteins c-bcl-2; Tumor Cells, Cultured

The structures of two novel 3,4-seco-lanostane-type triterpenes isolated from the sclerotium of Poria cocos were established to be 16alpha-hydroxy-3,4-seco-lanosta-4(28),8,24-triene-3,21-dioic acid (1; poricoic acid G) and 16alpha-hydroxy-3,4-seco-24-methyllanosta-4(28),8,24(24(1))-triene-3,21-dioic acid (2; poricoic acid H) on the basis of spectroscopic methods. These two, and eight other known compounds isolated from the sclerotium, poricoic acid B (3), poricoic acid A (4), tumulosic acid (5), dehydrotumulosic acid (6), 3-epidehydrotumulosic acid (7), polyporenic acid C (8), 25-hydroxy-3-epidehydrotumulosic acid (9), and dehydroabietic acid methyl ester (10), showed potent inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Evaluation of the cytotoxicity of compounds 1 and 4 against human cancer cell lines revealed that 1 was significantly cytotoxic to leukemia HL-60 cells [GI(50) (concentration that yields 50% growth) value 39.3 nM], although it showed only moderate cytotoxicity to the other cells. Compound 4 exhibited moderate cytotoxicity to all of the cancer cell lines tested.

Topics: Antineoplastic Agents, Phytogenic; Brain Neoplasms; Chromatography, High Pressure Liquid; Colonic Neoplasms; Drug Screening Assays, Antitumor; Female; Humans; Japan; Kidney Neoplasms; Lanosterol; Leukemia, Myeloid; Lung Neoplasms; Melanoma; Molecular Conformation; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Ovarian Neoplasms; Plants, Medicinal; Polyporaceae; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet; Triterpenes; Tumor Cells, Cultured

The effect of a mixture of vitamins in modifying the efficacy of commonly used drugs in the treatment of human melanoma has not been studied. Vitamin C and d-alpha-tocopheryl succinate (alpha-TS) alone reduced the growth of human melanoma (SK-30) cells in culture, whereas beta-carotene (BC), 13-cis-retinoic acid (RA), or sodium selenite alone was ineffective. RA caused morphological changes, as evidenced by flattening of cells and formation of short cytoplasmic processes. A mixture of four vitamins (vitamin C, BC, alpha-TS, and RA) was more effective in reducing growth of human melanoma cells than a mixture of three vitamins. The growth-inhibitory effect of cis-platin, decarbazine, tamoxifen, and recombinant interferon-alpha 2b was enhanced by vitamin C alone, a mixture of three vitamins (BC, alpha-TS, and RA), and a mixture of four vitamins (vitamin C, BC, alpha-TS, and RA) that contained 50 micrograms/ml of vitamin C. These data show that a mixture of three or four vitamins can enhance the growth-inhibitory effect of currently used chemotherapeutic agents on human melanoma cells.

Topics: Ascorbic Acid; beta Carotene; Carotenoids; Cell Division; Cisplatin; Dacarbazine; Drug Screening Assays, Antitumor; Humans; Interferon alpha-2; Interferon-alpha; Isotretinoin; Melanoma; Recombinant Proteins; Tamoxifen; Tocopherols; Tumor Cells, Cultured; Vitamin E; Vitamins

This study compares the toxic effects of the carotenoids, beta-carotene and canthaxanthin, and alpha-tocopherol (vitamin E) on human tumor cells and their normal counterparts in vitro. Seven different malignant cell lines were examined: oral carcinoma (two cell lines), breast (two cell lines), lung carcinoma (two cell lines), and malignant melanoma. The in vitro cell culture assays showed a consistent morphologic change in the affected tumor cells following treatment with carotenoid or vitamin E. A rounding of the tumor cells and eventual lifting off the tissue culture plate were observed. These changes were apparent after 1 to 5 hours of treatment depending on the tumor cell line. Associated with these observable cellular changes were quantitative reductions in proliferation (3H-thymidine proliferation) and succinic dehydrogenase activity (MTT assay). In addition, there was a noticeable change in protein expression, with an increased expression of a 70-kD protein following treatment with beta-carotene. This protein was associated with tumor cells showing a decrease in proliferation (oral carcinoma, malignant melanoma) but not with normal keratinocytes or melanocytes. These studies substantiate a selective cytotoxic effect on human tumor cell growth by carotenoids and alpha-tocopherol in vitro, and may provide an explanation of the therapeutic activity of these agents and their possible use in the treatment of premalignancy or early oral carcinoma.

Topics: beta Carotene; Breast Neoplasms; Canthaxanthin; Carcinoma, Squamous Cell; Carotenoids; Cell Division; Cells, Cultured; Electrophoresis, Polyacrylamide Gel; Humans; Keratinocytes; Lung Neoplasms; Melanocytes; Melanoma; Mouth Neoplasms; Neoplasm Proteins; Succinate Dehydrogenase; Tumor Cells, Cultured; Vitamin E

The effects of physiologic concentrations of conjugated linoleic acid (CLA) and beta-carotene were assessed on human (M21-HPB, malignant melanoma; HT-29, colorectal; MCF-7, breast) cancer cells. The incubation of cancer cells with CLA showed significant reductions in proliferation (18-100%) compared to control cultures. M21-HPB and MCF-7 cell mortality was dose- and time-dependent. beta-Carotene was inhibitory to breast cells only. MCF-7 cells supplemented with CLA incorporated significantly less [3H]leucine (45%), [3H]uridine (63%) and [3H]thymidine (46%) than control cultures. M21-HPB and HT-29 cells supplemented with CLA incorporated less [3H]leucine (25-30%). These in vitro results suggest that CLA and beta-carotene may be cytotoxic to human cancer cells in vivo.

Topics: beta Carotene; Breast Neoplasms; Carotenoids; Cell Division; Cell Line; Colonic Neoplasms; DNA, Neoplasm; Dose-Response Relationship, Drug; Female; Humans; Leucine; Linoleic Acids; Melanoma; Neoplasm Proteins; RNA, Neoplasm; Thymidine; Tritium; Tumor Cells, Cultured; Uridine

Dietary intake and the plasma levels of retinol, alpha-tocopherol, lycopene, alpha-carotene, and beta-carotene for 204 cases with malignant melanoma were compared with those of 248 controls. Cases and controls were patients 18 years of age or older making their first visit to a dermatology subspecialty clinic for pigmented lesions from July 1, 1982 to September 1, 1985. Intakes of nutrients were estimated using a semiquantitative food frequency questionnaire. No significant associations with malignant melanoma were observed for higher plasma levels of lycopene, retinol, or alpha-carotene in logistic regression analyses after controlling for age, sex, plasma lipids, and known constitutional risk factors (hair color and ability to tan). In similar models, the odds ratio comparing the highest with the lowest quintile was 0.9 (95% confidence interval (CI) 0.5-1.5) for plasma beta-carotene, 0.7 (95% CI 0.5-1.3) for plasma alpha-tocopherol, 0.7 (95% CI 0.4-1.2) for carotene intake, and 0.7 (95% CI 0.4-1.3) for total vitamin E intake. A trend toward reduced risk of melanoma was observed for increasing intake of iron (not including supplements); this was related to the more frequent consumption of baked goods, such as cake, among controls. Alcohol consumption was positively associated with risk of melanoma (chi for trend = 2.1, p = 0.03); the odds ratio for consumption of over 10 g/day compared with persons with no alcohol intake was 1.8 (95% CI 1.0-3.3).

Topics: Adult; Alcohol Drinking; beta Carotene; Carotenoids; Case-Control Studies; Diet; Female; Hair Color; Humans; Iron; Male; Melanoma; Middle Aged; Odds Ratio; Regression Analysis; Risk Factors; Smoking; Vitamin E

Several studies suggest that beta-carotene reduces the risk of some cancers. Except for its function as an antioxidant, the effect of this vitamin on mammalian cells remains poorly defined. This study was performed to show whether beta-carotene treatment of murine B-16 melanoma cells in culture induces differentiation and alters the adenylate cyclase (AC) system. The AC system mediates the action of agents which regulate cell differentiation and transformation. Results showed that beta-carotene treatment for a period of 24 hours or more caused morphological differentiation without changing the level of melanin, and reduced basal and melanocyte-stimulated hormone (MSH)-, sodium fluoride (NaF)-, and forskolin-stimulated AC activity in vitro. Retinol, a metabolite of beta-carotene, inhibited growth without morphological differentiation and reduced basal and MSH- and NaF-stimulated AC activity. However, butylated hydroxyanisole, a lipid-soluble antioxidant, also reduced growth without morphological differentiation, but it failed to alter basal or MSH-stimulated AC activity. The present and previous studies show that the AC system represents a common site where some antitumor-promoting vitamins (beta-carotene, retinol, retinoic acid, and alpha-tocopheryl succinate) act.

Topics: Adenylyl Cyclases; Animals; beta Carotene; Carotenoids; Cell Division; Cell Survival; Colforsin; Melanocyte-Stimulating Hormones; Melanoma; Mice; Sodium Fluoride; Tumor Cells, Cultured; Vitamin A