tannins and Skin-Neoplasms

Our research objective is to develop nontoxic cancer chemopreventive agents and to apply these agents in treating humans. We are identifying agents that inhibit the process of tumor promotion in two-stage carcinogenesis experiments on mouse skin.. We review (a) the inhibitory effect of penta-O-galloyl-beta-D-glucose (5GG) on tumor promotion by teleocidin, one of the 12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoters (5GG is structurally similar to (-)-epigallocatechin gallate (EGCG) and is isolated from hydrolyzed tannic acid); (b) the inhibitory effects of EGCG, the main constituent of Japanese green tea, on tumor promotion with two tumor promoters, teleocidin and okadaic acid, a non-TPA-type tumor promoter; (c) the mechanisms of action of EGCG, a single application of which reduced the specific binding of [3H]TPA and [3H]okadaic acid to a particulate fraction of mouse skin; and (d) the anticarcinogenic effects of EGCG on duodenal carcinogenesis induced by N-ethyl-N'-nitro-N-nitrosoguanidine in male C57BL/6 mice. EGCG is a nontoxic compound.. We believe that the main constituent of Japanese green tea, EGCG, is a practical cancer chemopreventive agent available in everyday life.

Topics: Animals; Anticarcinogenic Agents; Catechin; Hydrolyzable Tannins; Male; Mice; Mice, Inbred C57BL; Skin; Skin Neoplasms; Tannins; Tea; Tetradecanoylphorbol Acetate

Skin cancer is the most common malignancy in the world and also one of the major causes of death worldwide. The toxic environmental pollutant 7,12-dimethylbenz[a]anthracene (DMBA) is a skin-specific carcinogen. Tannic acid (TA) is reported to be effective against various types of chemical-induced toxicities and carcinogenesis as well. In the present study, we have evaluated the therapeutic potential of tannic acid in DMBA + croton oil-induced skin cancer in Swiss albino mice. Protective effect of TA against skin cancer was evaluated in terms of antioxidant enzymes activities, lipid peroxidation, histopathological changes and expression of inflammation and early tumour markers. DMBA + croton oil causes depletion of antioxidant enzymes (p < 0.001) and elevation of early inflammatory and tumour promotional events. TA prevents the DMBA + croton oil-induced toxicity through a protective mechanism that involves the reduction of oxidative stress as well as COX-2, i-NOS, PCNA protein expression and level of proinflammatory cytokine such as IL-6 release at a very significant level (p < 0.001). It could be concluded from our results that TA attenuates DMBA + croton oil-induced tumour promotional potential possibly by inhibiting oxidative and inflammatory responses and acts as antioxidant, anti-inflammatory and antiproliferative agent.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anticarcinogenic Agents; Croton; Cyclooxygenase 2; Disease Progression; Drug Evaluation, Preclinical; Female; Glutathione; Hydrogen Peroxide; Interleukin-6; Lipid Peroxidation; Mice; Nitric Oxide Synthase Type II; Plant Oils; Proliferating Cell Nuclear Antigen; Skin; Skin Neoplasms; Tannins; Xanthine Oxidase

The objective of this paper was to study the extraction methods of tannin constituents from Semen Cuscutae and their anti-papilloma effects. Single factor test and orthogonal design methods were used to determine the optimal extraction method; the mouse skin papilloma model induced by DMBA/croton oil was established, which was a classic two-stage carcinogenesis model being used to observe and evaluate the anti-carcinogenic effects of tannins extracted from Semen Cuscutae in different stages. The optimal extraction method of Semen Cuscutae was a 20-fold volume of solvent, a temperature of 50 °C, three times of extraction, with 20 min each, skin papilloma experiment revealed that the number of bearing tumors gradually reduced, and the inhibition rate gradually increased with the increase of dose, in the high-dose group, its inhibition rate reached 70.2%. Tannin extract from Semen Cuscutae has an obvious inhibitory effect on skin papilloma development.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Antineoplastic Agents, Phytogenic; Croton Oil; Cuscuta; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Male; Mice; Mice, Inbred Strains; Papilloma; Phytotherapy; Plant Extracts; Seeds; Skin Neoplasms; Tannins

The success of green tea as a cancer preventive is based on evidence that green tea contains tannins and antioxidants, does not show toxicity in humans and has long traditional use in Asia. In the light of this, herbal medicines are now also attracting attention as potential sources of cancer preventive agents. Using the inhibition of TNF-alpha release assay, we studied Acer nikoense (Megusurino-ki in Japanese), one of the herbal medicines. The inhibitory activity of TNF-alpha release was found in the leaf extract rather than the bark extract, and the main active constituents were identified as geraniin and corilagin, which are present in another Japanese traditional herb, Geranium thunbergii (Genno-shoko). The IC50 values of TNF-alpha release inhibition were 43 microM for geraniin and 76 microM for corilagin, whereas that for (-)-epigallocatechin gallate (EGCG) was 26 microM. Treatment with geraniin prior to application of okadaic acid, a tumor promoter on mouse skin initiated with 7,12-dimethylbenz(a)anthracene, reduced the percentage of tumor-bearing mice from 80.0 to 40.0% and the average numbers of tumor per mouse from 3.8 to 1.1 in week 20. Thus, geraniin has slightly weaker inhibitory activity than EGCG. Since geraniin and corilagin have been well investigated as representative tannins, we discuss here the new possibility of classical herbal medicine in the development of preventive agents for cancer and other life-style related diseases.

Topics: 3T3 Cells; 9,10-Dimethyl-1,2-benzanthracene; Animals; Anticarcinogenic Agents; Carcinogens; Chromatography, High Pressure Liquid; Glucosides; Hydrolyzable Tannins; Mice; Mice, Inbred BALB C; Plant Extracts; Plant Leaves; Plants, Medicinal; Skin Neoplasms; Tannins; Tumor Necrosis Factor-alpha

We recently showed that Tarapod tannic acid (TA), a hydrolyzable tannin extracted from the pods of the Tara tree (Caesalpinia spinosa), was more effective than other tannins tested at inhibiting ultraviolet-B (UV-B)-stimulated hydrogen peroxide activity (an indirect measure of free radicals) in the skin of hairless mice. We also found that Tarapod TA inhibited UV-B-induced ornithine decarboxylase activity and UV-B-stimulated DNA synthesis, two biochemical markers linked to the skin tumor-promoting ability of this physical carcinogen. For this reason, we examined the effect of topical application, force feeding (gavage), and intraperitoneal injections of Tarapod TA on mouse skin chronically treated with UV-B light. Mice were initiated by a single topical application of 7,12-dimethylbenz[a]anthracene (50 nmol) and promoted by two weekly treatments with UV-B light (250 mJ/cm2) for 25 weeks. Topical application of Tarapod TA, 20 minutes before irradiation, resulted in a dose-dependent inhibition of tumor incidence (number of mice with tumors) and tumor yield (number of tumors/mouse), with 8 mg of TA inhibiting tumor yield by 70% at Week 25. Intraperitoneal injections of low doses (10 mg/kg mouse body wt), but not of high doses (25 mg/kg body wt), of TA afforded protection against UV-B-induced papillomas. However, the protection by intraperitoneal injection was lower than that observed by topical application: 10 mg/kg body wt of TA reduced tumor yield by 55%. The force feeding of 10 mg of Tarapod TA before irradiation failed to significantly inhibit the yield of tumors at the end of the experiment but delayed tumor appearance by six weeks. These results suggest that plant tannins administered topically or injected intraperitoneally reduce the tumor-promoting effects of UV-B radiation and thus could be useful photoprotectants.

Topics: Administration, Oral; Administration, Topical; Animals; Antineoplastic Agents, Phytogenic; Female; Injections, Intraperitoneal; Mice; Mice, Hairless; Neoplasms, Radiation-Induced; Phytotherapy; Plant Extracts; Radiation-Protective Agents; Skin; Skin Neoplasms; Tannins; Trees; Ultraviolet Rays

The anti-oxidant and the anti-tumor-promotion activities of several hydrolyzable tannins (HTs), including a commercial tannic-acid (TA) mixture, were examined in mouse skin treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) in vivo. A single application of TPA gradually increases the hydroperoxide (HPx)-producing activity of the epidermis, which is maximally stimulated at 3 days and returns to control levels at 9 days. Pre-treatments with TA and ellagic acid (EA) strongly inhibit, in a dose-dependent manner, this HPx response to TPA. Total inhibition by TA lasts for about 16 hr, beyond which it is substantially reduced but not completely lost. TA can also reduce the level of epidermal HPx when it is applied 36 hr after the tumor promoter. EA is an antioxidant 10 times more potent than TA and n-propyl gallate (PG), which are equally effective against TPA-induced HPx production. Gallic acid is the least effective of the HTs in inhibiting HPx formation. TA also inhibits the production of HPx induced by several structurally different tumor promoters and the greater HPx responses produced by repeated TPA treatments. When applied 20 min before each promotion treatment, twice a week for 45 weeks, several HTs inhibit the incidence and yield of papillomas and carcinomas promoted by TPA in initiated skin. Overall, TA is more effective than EA and PG in inhibiting skin-tumor promotion by TPA, suggesting that the anti-oxidant effects of HTs are essential but not sufficient for their anti-tumor-promotion activity.

Topics: Animals; Dose-Response Relationship, Drug; Female; Hydrogen Peroxide; Mice; Skin; Skin Neoplasms; Tannins; Tetradecanoylphorbol Acetate

Tannic acid, a naturally occurring dietary polyphenol, was evaluated as a possible anticarcinogen in an initiation-and-promotion skin tumorigenesis protocol. In the 2-stage tumor protocol in SENCAR mice, using DMBA, BP and MNU as the initiating agents followed by twice-weekly applications of TPA as tumor promotor, tannic acid was found to be an effective inhibitor of tumor formation whether the tumor data are considered as cumulative number of tumors, percentage of mice with tumors or tumors/mouse. After 9 weeks of TPA application, the number of tumors/mouse in the groups receiving DMBA, BP and MNU were 32.10 +/- 3.18, 3.70 +/- 0.55 and 2.00 +/- 0.53, respectively, whereas the corresponding numbers in the DMBA, BP and MNU groups receiving prior applications of tannic acid were 11.50 +/- 2.38, 0.35 +/- 0.15 and 0.35 +/- 0.13, respectively. These results suggest that tannic acid may prove useful in reducing the risk of chemically-induced skin tumorigenesis.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Administration, Cutaneous; Animals; Antineoplastic Agents, Phytogenic; Benzo(a)pyrene; Female; Hydrolyzable Tannins; Methylnitrosourea; Mice; Skin Neoplasms; Tannins

Tannic acid inhibits the mutagenicity of several polycyclic aromatic hydrocarbons (PAHs) and their bay-region diol-epoxides. Our prior studies have shown that when applied topically to Sencar mice, tannic acid caused substantial inhibition of epidermal PAH metabolism, subsequent PAH-DNA adduct formation, and PAH-induced skin tumorigenesis (H. Mukhtar et al., Cancer Res., 48:2361-2365, 1988, and references therein). In this study the effects of tannic acid supplementation in the diet (1%, w/w, in AIN-76 diet) of Sencar mice on benzo(a)pyrene (BP) metabolism and its subsequent DNA binding and tumorigenesis in lung and forestomach were evaluated. Animals receiving a tannic acid-containing diet showed diminished aryl hydrocarbon hydroxylase and 7-ethoxy-resorufin O-deethylase activities in the forestomach and lung. Elevated glutathione S-transferase and NAD(P)H:quinone reductase activities were observed in these tissues. Maximum effects occurred after 45 days of feeding. Administration of [3H]BP p.o. to animals resulted in lower covalent binding to DNA in forestomach and lung of animals receiving tannic acid-containing diet as compared to animals receiving AIN-76 control diet. Tumor induction studies in forestomach and lung revealed significant protection against BP-induced tumorigenesis in animals fed tannic acid-supplemented diet as compared to animals fed control diet. The mice fed tannic acid-supplemented diet developed 3.3 forestomach tumors/mouse compared to 5.2 tumors/mouse in animals receiving control diet. The numbers of pulmonary tumors per mouse in animals fed tannic acid-supplemented diet and control diet were 1.6 and 3.1, respectively. Topical application of 7,12-dimethylbenz(a)anthracene to animals fed tannic acid-supplemented diet did not result in significant protection against skin tumorigenesis. However, a slight delay in the onset of skin tumor formation occurred in tannic acid-fed animals when compared to animals receiving control diet. Our data suggest that dietary supplementation with tannic acid affords protection against BP-induced forestomach and lung tumorigenesis in rodents.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Aryl Hydrocarbon Hydroxylases; Benzo(a)pyrene; Cytosol; Diet; DNA; DNA Adducts; Female; Gastric Mucosa; Hydrolyzable Tannins; Lung; Lung Neoplasms; Mice; Microsomes; Skin; Skin Neoplasms; Stomach; Stomach Neoplasms; Tannins

Our recent studies have shown that naturally occurring dietary plant phenols such as tannic acid, quercetin, myricetin, and anthraflavic acid are capable of inhibiting polycyclic aromatic hydrocarbon (PAH) metabolism and subsequent PAH-DNA adduct formation in epidermis of SENCAR mice (M. Das, et al., Cancer Res., 47: 760-766, 1987, and 47: 767-773, 1987). In this study these plant phenols were tested for their effects against PAHs and N-methyl-N-nitrosourea-induced skin tumorigenesis in mice. Each plant phenol was evaluated as a possible anticarcinogen in an initiation and promotion and a complete skin tumorigenesis protocol. In the two-stage tumor protocol in SENCAR mice using 7,12-dimethylbenz(a)anthracene, benzo(a)pyrene, and N-methyl-N-nitrosourea as the initiating agent followed by twice weekly applications of 12-O-tetradecanoylphorbol-13-acetate as tumor promoter each plant phenol afforded significant protection against skin tumorigenicity. The protective effects were verified both by prolongation of latency period and by subsequent tumor development. In the complete carcinogenesis protocol in BALB/c mice using 3-methylcholanthrene as a tumorigen the applications of each of the plant phenols 30 min prior to each PAH application afforded significant protection by delaying the onset and the subsequent development of skin tumors. Our results suggest that these plant phenols have substantial though variable potential for modifying the risk of skin tumorigenicity induced by a wide variety of chemicals and of these tannic acid was shown to have maximal chemoprotective effects.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Administration, Topical; Animals; Anthraquinones; Benzo(a)pyrene; DNA; Female; Flavonoids; Hydrolyzable Tannins; Methylcholanthrene; Methylnitrosourea; Mice; Mice, Inbred BALB C; Quercetin; Skin Neoplasms; Tannins

Topics: Animals; Carcinogens; Citrus; Eucalyptus; Latex; Microspheres; Oils, Volatile; Papilloma; Plants, Medicinal; Rats; Rubber; Skin Neoplasms; Tannins; Terpenes; Turpentine