1-1-diphenyl-2-picrylhydrazyl and Skin-Neoplasms

Topics: Antineoplastic Agents; Biphenyl Compounds; Cell Line, Tumor; Cell Survival; Doxorubicin; Drug Synergism; Glycolipids; Humans; Impatiens; Melanoma; Monophenol Monooxygenase; Mutagenicity Tests; Picrates; Skin Neoplasms; Vibrio

Topics: Agaricales; Animals; Biphenyl Compounds; Chick Embryo; Enzyme Inhibitors; Melanins; Melanoma, Experimental; Methimazole; Mice; Monophenol Monooxygenase; Picrates; Pyrones; Skin; Skin Neoplasms; Tumor Cells, Cultured

Lichens are considered a great bio-resource because they produce large numbers of secondary metabolites with many biological activities; however, they have not been cultivated under artificial conditions to date. As a result, lichen substances from natural sources are limited and have not been widely utilized in commercial applications. Accordingly, interest in lichen-associated fungi, especially endogenic fungi, has increased. Ultraviolet (UV) radiation in sunlight is harmful to human health, resulting in demand for effective UV filtering agents for use in sunscreen. In this study, we purified (3

Topics: Animals; Anti-Infective Agents; Antioxidants; Ascorbic Acid; Biphenyl Compounds; Butylated Hydroxyanisole; Candida albicans; Cell Line; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Isocoumarins; Keratinocytes; Lichens; Lipid Peroxidation; Melanins; Melanoma, Experimental; Mice; Picrates; Saccharomycetales; Skin Neoplasms; Sunscreening Agents; Superoxides

Luteolin is a naturally occurring flavonoid present in many plants with diverse applications in pharmacology. Despite several studies elucidating its significant anti-cancer activity against various cancer cells, the mechanism of action in skin cancer is not well addressed. Hence, we investigated the effects of luteolin in HaCaT (human immortalized keratinocytes) and A375 (human melanoma) cells. The radical scavenging abilities of luteolin were determined spectrophotometrically, prior to a cytotoxic study (XTT assay). Inhibitory effects were assessed by colony formation assay. Further, the capability of luteolin to induce cell cycle arrest and apoptosis were demonstrated by flow cytometry and cellular DNA fragmentation ELISA, respectively. The results revealed that luteolin possesses considerable cytotoxicity against both HaCaT and A375 cells with IC50 values of 37.1 μM and 115.1 μM, respectively. Luteolin also inhibited colony formation and induced apoptosis in a dose and time-dependent manner by disturbing cellular integrity as evident from morphological evaluation by Wright- Giemsa staining. Accumulation of cells in G2/M (0.83-8.14%) phase for HaCaT cells and G0/G1 (60.4-72.6%) phase for A375 cells after 24 h treatment indicated cell cycle arresting potential of this flavonoid. These data suggest that luteolin inhibits cell proliferation and promotes cell cycle arrest and apoptosis in skin cancer cells with possible involvement of programmed cell death, providing a substantial basis for it to be developed into a potent chemopreventive template for skin cancer.

Topics: Apoptosis; Biphenyl Compounds; Cell Line, Tumor; Cell Proliferation; Cell Survival; DNA Fragmentation; Free Radical Scavengers; Free Radicals; G1 Phase Cell Cycle Checkpoints; Humans; Iron; Keratinocytes; Luteolin; M Phase Cell Cycle Checkpoints; Melanoma; Picrates; Skin Neoplasms

Solar ultraviolet radiation (UV) is a major cause of non-melanoma skin cancer in humans. Photochemoprevention with natural products represents a simple but very effective strategy in the management of cutaneous neoplasia. The study investigated the protective activity of Calluna vulgaris (Cv) and red grape seeds (Vitis vinifera L, Burgund Mare variety) (BM) extracts in vivo on UVB-induced deleterious effects in SKH-1 mice skin. Forty SKH-1 mice were randomly divided into 4 groups (n=10): control, UVB irradiated, Cv + UVB irradiated, BM+UVB irradiated. Both extracts were applied topically on the skin in a dose of 4 mg/40 μl/cm(2) before UVB exposure - single dose. The effects were evaluated in skin 24 hours after irradiation through the presence of cyclobutane pyrimidine dimers (CPDs) and sunburn cells, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6 levels. The antioxidant activity of BM extract was higher than those of Cv extract as determined using stable free radical DPPH assay and ABTS test. One single dose of UVB generated formation of CPDs (p<0.0001) and sunburn cells (p<0.0002) and increased the cytokine levels in skin (p<0.0001). Twenty hours following irradiation BM extract inhibited UVB-induced sunburn cells (p<0.02) and CPDs formation (p<0.0001). Pretreatment with Cv and BM extracts resulted in significantly reduced levels of IL-6 and TNF-α compared with UVB alone (p<0.0001). Our results suggest that BM extracts might be a potential candidate in preventing the damages induced by UV in skin.

Topics: Animals; Apoptosis; Biphenyl Compounds; Calluna; Cytokines; Disease Models, Animal; Female; Free Radical Scavengers; Humans; Mice; Mice, Hairless; Phytotherapy; Picrates; Plant Extracts; Pyrimidine Dimers; Random Allocation; Seeds; Skin; Skin Neoplasms; Sunburn; Ultraviolet Rays; Vitis

Resveratrol, sesamol, sesame oil and sunflower oil are known natural dietary components with intrinsic cancer chemopreventive potentials. As a part of our study of dietary constituents as potential cancer chemopreventive agents, we have assessed the anti-cancer potentials of these products in the promotion stage of cancer development employing the in vitro Epstein-Barr virus early antigen activation assay induced by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). Further, we studied the activities of these compounds in the brine shrimp cytotoxicity assay as well as on the stable 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging bioassay with a view to comparing some of the mechanisms of their anti-cancer activity. Finally, we compared the observed chemoprotective capabilities of the four products in the in vivo 7,12 dimethylbenz(a)anthracene initiated and TPA-promoted mouse skin two-stage carcinogenesis protocols. All the products tested showed a profound inhibitory effect on the Epstein-Barr virus early antigen induction using Raji cells. Comparatively, sesame oil was the most potent followed by sesamol and then resveratrol. Only sesamol and resveratrol showed a remarkable cytotoxic activity in the brine shrimp lethality assays as well as profound free radical scavenging activity in the DPPH bioassay. In both test systems, sesamol exhibited a more remarkable activity than resveratrol while sesame oil and sunflower oil did not exhibit any appreciable activity even at the highest concentrations tested (4000 microg ml(-1) ). In our in vivo assay at a 50-fold molar ratio to TPA, sesamol offered 50% reduction in mouse skin papillomas at 20 weeks after promotion with TPA. Under an identical molar ratio to TPA, resveratrol offered a 60% reduction in the papillomas in mouse at 20 weeks. Thus sesamol seems to be an almost equally potent chemopreventive agent. Sesame oil and sunflower oil offered 20 and 40% protection, respectively, in the mouse skin tumor model. The anti-oxidant capabilities of these compounds could not solely explain the observed anti-cancer characteristics. Resveratrol is present in grapes. Sesamol, a constituent of sesame oil and sunflower oil are regularly consumed dietary natural products. The observed chemopreventive effect of these products particularly warrants more attention since they already exist in the population with no known adverse effects.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Antigens, Viral; Antineoplastic Agents, Phytogenic; Artemia; Benzodioxoles; Biphenyl Compounds; Cocarcinogenesis; Female; Free Radical Scavengers; Herpesvirus 4, Human; Lethal Dose 50; Mice; Mice, Inbred ICR; Phenols; Picrates; Plant Oils; Resveratrol; Sesame Oil; Skin Neoplasms; Stilbenes; Sunflower Oil; Tetradecanoylphorbol Acetate; Tumor Cells, Cultured; Virus Activation

Salvia miltiorrhiza is a traditional Chinese medicine which has been well documented for its anti-cancer effects. Based on the structure of danshinone, one of the active compounds derived from Salvia miltiorrhiza, we synthesized a simplified phenolic analog, S-3-1, and tried to explore its possible actions in preventing the development of cancer. With the Ames test, S-3-1 was found to efficiently suppress the mutagenicity of benzo[alpha]pyrene. This result is consistent with the inhibitory effect of S-3-1 on the activation of benzo[alpha]pyrene by hepatic microsomal enzymes. Besides the anti-initiation effects, S-3-1 could significantly inhibit the croton oil-induced increase of mouse skin epithermal ornithine decarboxylase activity. Moreover, S-3-1 quenched both superoxide and hydroxyl free radicals whereas it inhibited lipid peroxidation in the in vitro model. These results suggest that S-3-1 might act as anti-initiation and anti-promotion agents through reversing the biochemical alterations induced by carcinogen during carcinogenesis. Therefore, we further investigated the effects of S-3-1 on carcinogenesis. In vitro, S-3-1 inhibited the benzo[alpha]pyrene-induced transformation of V79 Chinese hamster lung fibroblasts. At 10-40 mg/kg, S-3-1 was found to inhibit the development of DMBA/croton oil-induced skin papilloma in mice through decreasing the incidence of papilloma, prolonging the latent period of tumor occurrence and reducing tumor number per mouse in a dose-dependent manner. We concluded from this study that S-3-1 might be developed as a new chemopreventive drug.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anticarcinogenic Agents; Benzo(a)pyrene; Benzofurans; Bepridil; Biphenyl Compounds; Cell Transformation, Neoplastic; Cells, Cultured; Cricetinae; Croton Oil; Cysteine; Disease Models, Animal; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Epithelial Cells; Fibroblasts; Free Radical Scavengers; Hypoxanthine; In Vitro Techniques; Iron; Lipid Peroxidation; Lung; Male; Medicine, Chinese Traditional; Mice; Mice, Inbred ICR; Microsomes, Liver; Molecular Structure; Mutagens; Ornithine; Ornithine Decarboxylase; Papilloma; Pentetic Acid; Phenanthrenes; Picrates; Plants, Medicinal; Rats; Salmonella; Skin; Skin Neoplasms; Spectrometry, Mass, Electrospray Ionization; Structure-Activity Relationship; Xanthine Oxidase

The in vitro antioxidative activities of various kinds of vinegar were investigated by using a linoleic acid autoxidation model detected by the thiobarbituric acid (TBA) method and the 1,1-diphenyl-2-picrylhydrazyl radical system. An ethyl acetate extract of Kurosu (EK), a vinegar made from unpolished rice, exhibited the highest antioxidative activity in both systems. EK (5 mg) inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced edema formation (14%) and myeloperoxidase activity (52%, P< 0.01) in female ICR mouse skin. Furthermore, EK significantly suppressed double TPA application-induced H2O2 generation (53%, P< 0.01) and lipid peroxidation determined by the TBA-reacting substance level (95 %, P< 0.01). In a two-stage carcinogenesis experiment with dimethylbenz[a]anthracene/TPA, EK significantly reduced the number of tumors per mouse by 36% (P<0.05) at 15 weeks after promotion. These results suggest that the antitumor-promoting effect may be partially due to the antioxidative properties of EK such as the decomposition of free radicals and interference with free radical-generating leukocytes.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Acetic Acid; Animals; Antioxidants; Bepridil; Biphenyl Compounds; Edema; Female; Free Radical Scavengers; Free Radicals; Hydrogen Peroxide; Inflammation; Lipid Peroxidation; Mice; Mice, Inbred ICR; Oryza; Picrates; Skin; Skin Neoplasms; Tetradecanoylphorbol Acetate; Thiobarbituric Acid Reactive Substances; Time Factors; Vitamin E