title: Antiprotease and antimetastatic activity of ursolic acid isolated from Salvia officinalis.
abstract: Proteases play a regulatory role in a variety of pathologies including cancer, pancreatitis, thromboembolic disorders, viral infections and many others. One of the possible strategies how to combat with these pathologies seems to be the use of low molecular inhibitors. Natural products were evaluated in the in vitro antiprotease assay on serine proteases (trypsin, thrombin and urokinase) and on the cysteine protease cathepsin B. We found interesting results for beta-ursolic acid isolated from Salvia officinalis, which significantly inhibited all tested proteases in vitro in the micromolar range. beta-Ursolic acid showed the strongest inhibition activity to urokinase (IC50 = 12 microM) and cathepsin B (IC50 = 10 microM) as proteases included in tumour invasion and metastasis indicated possible anticancer effectivity. Therefore, we tested the ability of beta-ursolic acid at doses of 50, 75 and 100 mg/kg given i.p. to inhibit lung colonization of beta16 mouse melanoma cells in vivo. We found, that beta-ursolic acid significantly decreased the number of B16 colonies in the lungs of mice at the dose 50 mg/kg (p < 0.05).
authors.affiliation: Institute of Molecular Physiology and Genetics, Vlárska 5, Bratislava 83334, Slovakia. andrejjedinak@orangemail.sk
authors.forename: Andrej
authors.initials: A
authors.lastname: Jedinák
authors.forename: Marta
authors.initials: M
authors.lastname: Mucková
authors.forename: Daniela
authors.initials: D
authors.lastname: Kost'álová
authors.forename: Tibor
authors.initials: T
authors.lastname: Maliar
authors.forename: Irena
authors.initials: I
authors.lastname: Masterova
mesh_terms: D000470:Alkaloids / Q000302:isolation & purification; D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D005419:Flavonoids / Q000302:isolation & purification; D008297:Male; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D010946:Plants, Medicinal; D011480:Protease Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D027543:Salvia officinalis; D012878:Skin Neoplasms; D014315:Triterpenes / Q000302:isolation & purification* / Q000494:pharmacology; D000097245:Ursolic Acid
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D005419:Flavonoids; D011480:Protease Inhibitors; D014315:Triterpenes; D000097245:Ursolic Acid