Inhibition of skin tumorigenesis by Rosemary and its constituents carnosol and ursolic acid

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 initia...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1994-02, Vol.54 (3), p.701-708
Main Authors: MOU-TUAN HUANG, CHI-TANG HO, ZHI YUAN WANG, FERRARO, T, YOU-RONG LOU, STAUBER, K, WEI MA, GEORGIADIS, C, LASKIN, J. D, CONNEY, A. H
Format: Article
Language:English
Subjects:
9,10-Dimethyl-1,2-benzanthracene - antagonists & inhibitors
Abietanes
Animals
Anticarcinogenic Agents - therapeutic use
Antioxidants - toxicity
Arachidonic Acid - antagonists & inhibitors
Benzo(a)pyrene - antagonists & inhibitors
Benzo(a)pyrene - metabolism
Biological and medical sciences
Dermatitis, Contact - etiology
Dermatitis, Contact - prevention & control
DNA - metabolism
Drug Interactions
Enzyme Induction
Epidermis - drug effects
Epidermis - enzymology
Epidermis - metabolism
Female
General pharmacology
Hyperplasia
Magnoliopsida
Medical sciences
Mice
Mice, Inbred Strains
Ornithine Decarboxylase - drug effects
Ornithine Decarboxylase - metabolism
Pharmacognosy. Homeopathy. Health food
Pharmacology. Drug treatments
Phenanthrenes - therapeutic use
Plant Extracts - therapeutic use
Skin - drug effects
Skin - metabolism
Skin - pathology
Skin Neoplasms - chemically induced
Skin Neoplasms - prevention & control
Spices
Tetradecanoylphorbol Acetate - pharmacology
Triterpenes - therapeutic use
Tritium
Ursolic Acid
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Summary: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%.
ISSN:0008-5472
1538-7445