phytosterols and Skin-Neoplasms

A cream formulation containing high concentrations (10%) of a standard mixture of solasodine glycosides (BEC) has been shown to be effective in the treatment of malignant and benign human skin tumours. We now report that a preparation (Curaderm) which contains very low concentrations of BEC (0.005%) is effective in the treatment of keratoses, basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) of the skin of humans. In an open study, clinical and histological observations indicated that all lesions (56 keratoses, 39 BCCs and 29 SCCs) treated with Curaderm had regressed. A placebo formulation had no effect on a smaller number of treated lesions. Curaderm had no adverse effect on the liver, kidneys or haematopoietic system.

Topics: Administration, Topical; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Glycosides; Humans; Keratosis; Pharmaceutical Vehicles; Phytosterols; Precancerous Conditions; Skin Neoplasms; Solanaceous Alkaloids

The chemopreventive potential of cycloartenol on benzoyl peroxide and UVB radiation-induced cutaneous tumor promotion markers and oxidative stress in murine skin is assessed. Benzoyl peroxide treatment (20 mg/animal/0.2 ml acetone) and UVB radiation (0.420 J/m(2)/s) caused a decrease in the activities of cutaneous antioxidant enzymes namely, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase, phase II metabolizing enzyme such as glutathione-S-transferase and quinone reductase and depletion in the level of cutaneous glutathione. There was also enhancement in cutaneous microsomal lipid peroxidation, xanthine oxidase activity, [(14)C]-ornithine decarboxylase activity and [(3)H]-thymidine incorporation into cutaneous DNA. Cycloartenol was topically applied prior to the application of benzoyl peroxide at dose levels of 0.2 mg and 0.4 mg/kg body weight in acetone, which resulted in significant inhibition of epidermal ornithine decarboxylase activity and DNA synthesis (P < 0.001). There was also significant reduction of lipid peroxidation and xanthine oxidase activity (P < 0.001). In addition, the depleted levels of glutathione, inhibited activities of antioxidant and phase II metabolizing enzymes, were also recovered to a significant level (P < 0.001). The data indicate that cycloartenol is an effective chemopreventive agent in skin carcinogenesis.

Topics: Animals; Anticarcinogenic Agents; Benzoyl Peroxide; Biomarkers, Tumor; Catalase; Cytosol; Female; Glucosephosphate Dehydrogenase; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Glutathione Transferase; Lipid Peroxidation; Mice; Microsomes; Neoplasms, Radiation-Induced; Oxidative Stress; Phytosterols; Skin; Skin Neoplasms; Subcellular Fractions; Triterpenes; Ultraviolet Rays; Xanthine Oxidase

Inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice was observed in the methanol extract of rice bran and gamma-oryzanol. The active components of rice bran, sitosterol ferulate, 24-methylcholesterol ferulate, cycloartenol ferulate and 24-methylenecycloartanol ferulate inhibited markedly the TPA-induced inflammation in mice. The 50% inhibitory dose of these compounds for TPA-induced inflammation was 0.2-0.3 mg/ear. Furthermore, cycloartenol ferulate markedly inhibited the tumor-promoting effect of TPA in 7,12-dimethylbenz[a]anthracene-initiated mice.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anticarcinogenic Agents; Carcinogens; Cocarcinogenesis; Dermatitis, Contact; Female; Hypolipidemic Agents; Mice; Mice, Inbred ICR; Oryza; Phenylpropionates; Phytosterols; Plant Extracts; Skin; Skin Neoplasms; Sterols; Tetradecanoylphorbol Acetate; Triterpenes

A single topical application of 1 microgram of 12-O-tetradecanoylphorbol- 13-acetate (TPA) to the ears of mice was shown to induce edema, and this TPA-induced inflammation was inhibited by 4-methylsterol and triterpene derivatives. The ED50 of these compounds against TPA-induced inflammation was 0.1-3 mumol. Phytosterols had only slight inhibitory effects. Furthermore, application of 5 micrograms TPA to mouse skin rapidly caused accumulation of ornithine decarboxylase (ODC). Similarly, sitosterol and lupane-type triterpene derivatives markedly inhibited this TPA-induced ODC accumulation. In addition, 5 mumol betulinic acid markedly inhibited the promoting effect of 2.5 micrograms TPA applied twice weekly on skin tumor formation in mice initiated with 50 micrograms of 7,12-dimethylbenz[a]anthracene, and 5 mumol of sitosterol caused slight suppression. Thus, the inhibitory effects of sterol and triterpene derivatives on TPA-induced inflammation roughly parallelled their inhibitory activities against tumor promotion.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Antineoplastic Agents, Phytogenic; Betulinic Acid; Female; Mice; Mice, Inbred ICR; Ornithine Decarboxylase; Pentacyclic Triterpenes; Phytosterols; Sitosterols; Skin Neoplasms; Tetradecanoylphorbol Acetate; Triterpenes

Topics: Animals; Benz(a)Anthracenes; Carcinogens; Chemical Phenomena; Chemistry; Chromatography; Chromatography, Gas; Female; Freeze Drying; Hydrogen-Ion Concentration; Mice; Neoplasms, Experimental; Nicotiana; Nitrates; Phytosterols; Plants, Toxic; Polycyclic Compounds; Skin Neoplasms; Smoke; Terpenes