carnosol and Skin-Neoplasms

Carnosol is a natural compound extracted from rosemary and sage, which has been demonstrated to have anti-inflammatory, anti-oxidant, and anti-cancer properties. In this report, we evaluated the therapeutic potential and elucidated the potential mechanism of action of carnosol in chemoprevention of ultraviolet B-light (UVB) induced non-melanoma skin cancer formation. Our data indicated that carnosol could partially reduce UVB-induced reactive oxygen species (ROS) elevation and thus reduce DNA damage. It could also reduce UVB-induced formation of cyclobutane pyrimidine dimers (CDP) in keratinocytes possibly through its ability in absorbing UVB radiation. In addition, carnosol could inhibit the UVB-induced activation of NF-κB and also reduce UVB-induced transformation of keratinocytes. Taken together, the results indicate the role of carnosol as a potential chemopreventive agent upon UVB radiation.

Topics: Abietanes; Cell Line; Chemoprevention; DNA Damage; Humans; Keratinocytes; Neoplasms, Radiation-Induced; NF-kappa B; Reactive Oxygen Species; Rosmarinus; Salvia officinalis; Skin Neoplasms; Ultraviolet Rays

To compare the genoprotective and radioprotective effect of carnosol (COL) against damage induced by ionizing radiation with similar effects produced by different antioxidant compounds.. The genoprotective effect was studied by means of the micronucleus test for antimutagenic activity in which the reduction in the frequency of micronuclei was evaluated in cytokinesis-blocked cells of human lymphocytes. The radioprotective effects were studied by cell viability test (MTT) in PNT2 (normal prostate) and B16F10 (melanoma) cell lines when they were administered before exposure to different X-ray doses (4, 6, 8, 10 and 0 Gy).. Carnosol shows a significant genoprotective capacity (p < 0.001) against radiation with a protection factor of 50 %, and a dose-reduction factor of 4.3. Cell survival obtained with COL administered before exposure to 10 Gy of X-rays showed a protection factor of 55.1 %, eliminating 39 % of radiation-induced cell death in normal epithelial cells of prostate (PNT2) (p < 0.001). However, in the melanoma cell lines (B16F10) assayed, COL acted not as a radioprotector, but as a sensitizing agent increasing the cellular death by 34 % (p < 0.01) and producing an enhancement ratio of 2.12.. Carnosol may be developed as a radioprotective agent in the non-tumoral cells. However, in the B10F16 melanoma cells, melanogenesis is activated by COL leading to redistribution of the enzymatic balances of glutathione and cysteine-lyase production, which could compromise the intracellular redox defence system. This effect appears as an increase in the capacity of ionizing radiation-induced damage, and thus exhibits a paradoxical protective effect of COL on melanoma cells.

Topics: Abietanes; Animals; Antioxidants; Cell Line, Tumor; Cell Survival; Dose-Response Relationship, Radiation; Glutathione; Humans; Lymphocytes; Melanoma; Melanoma, Experimental; Mice; Micronucleus Tests; Oxidation-Reduction; Radiation-Protective Agents; Radiation-Sensitizing Agents; Radiation, Ionizing; Skin Neoplasms; Translational Research, Biomedical

A methanol extract of the leaves of the plant Rosmarinus officinalis L. (rosemary) was evaluated for its effects on tumor initiation and promotion in mouse skin. Application of rosemary to mouse skin inhibited the covalent binding of benzo(a)pyrene [B(a)P] to epidermal DNA and inhibited tumor initiation by B(a)P and 7,12-dimethylbenz[a]anthracene (DMBA). Topical application of 20 nmol B(a)P to the backs of mice once weekly for 10 weeks, followed 1 week later by promotion with 15 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) twice weekly for 21 weeks, resulted in the formation of 7.1 tumors per mouse. In a parallel group of animals that were treated topically with 1.2 or 3.6 mg of rosemary 5 min prior to each application of B(a)P, the number of tumors per mouse was decreased by 54 or 64%, respectively. Application of rosemary to mouse skin also inhibited TPA-induced ornithine decarboxylase activity, TPA-induced inflammation, arachidonic acid-induced inflammation, TPA-induced hyperplasia, and TPA-induced tumor promotion. Mice initiated with 200 nmol DMBA and promoted with 5 nmol TPA twice weekly for 19 weeks developed an average of 17.2 skin tumors per mouse. Treatment of the DMBA-initiated mice with 0.4, 1.2, or 3.6 mg of rosemary together with 5 nmol TPA twice weekly for 19 weeks inhibited the number of TPA-induced skin tumors per mouse by 40, 68, or 99%, respectively. Topical application of carnosol or ursolic acid isolated from rosemary inhibited TPA-induced ear inflammation, ornithine decarboxylase activity, and tumor promotion. Topical application of 1, 3, or 10 mumol carnosol together with 5 nmol TPA twice weekly for 20 weeks to the backs of mice previously initiated with DMBA inhibited the number of skin tumors per mouse by 38, 63, or 78%, respectively. Topical application of 0.1, 0.3, 1, or 2 mumol ursolic acid together with 5 nmol TPA twice weekly for 20 weeks to DMBA-initiated mice inhibited the number of tumors per mouse by 45-61%.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Abietanes; Animals; Anticarcinogenic Agents; Antioxidants; Arachidonic Acid; Benzo(a)pyrene; Dermatitis, Contact; DNA; Drug Interactions; Enzyme Induction; Epidermis; Female; Hyperplasia; Magnoliopsida; Mice; Mice, Inbred Strains; Ornithine Decarboxylase; Phenanthrenes; Plant Extracts; Skin; Skin Neoplasms; Spices; Tetradecanoylphorbol Acetate; Triterpenes; Tritium; Ursolic Acid