title: Evaluation of pentacyclic triterpenes found in Perilla frutescens for inhibition of skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate.
abstract: A series of pentacyclic tritperpenes found in Perilla frutescens (P. frutescens), including ursolic acid (UA), oleanolic acid (OA), corosolic acid (CA), 3-epi-corosolic acid (3-epiCA), maslinic acid (MA), and 3-epi-maslinic acid (3-epiMA) were evaluated for their effects on epidermal cell signaling, proliferation, and skin inflammation in relation to their ability to inhibit skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) and compared to UA as the prototype compound. All compounds were given topically 30 min prior to each TPA application and significantly inhibited skin tumor promotion. 3-epiCA and MA were significantly more effective than UA at inhibiting tumor development. All of these compounds significantly inhibited epidermal proliferation induced by TPA, however, CA, 3-epiCA and MA were more effective than UA. All compounds also reduced skin inflammation (assessed by infiltration of mast cells and T-cells) and inflammatory gene expression induced by TPA, however, 3-epiCA and MA were again more effective than UA. The greater ability of 3-epiCA and MA to inhibit skin tumor promotion was associated with greater reduction of Cox-2 and Twist1 proteins and inhibition of activation (i.e., phosphorylation) of IGF-1R, STAT3 and Src. Further study of these compounds, especially 3-epiCA and MA, for chemopreventive activity in other cancer model systems is warranted.
authors.affiliation: Division of Pharmacology and Toxicology in College of Pharmacy, The University of Texas at Austin, Austin, TX, USA.
authors.forename: Jiyoon
authors.initials: J
authors.lastname: Cho
authors.affiliation: Division of Pharmacology and Toxicology in College of Pharmacy, The University of Texas at Austin, Austin, TX, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Tremmel
authors.affiliation: Division of Pharmacology and Toxicology in College of Pharmacy, The University of Texas at Austin, Austin, TX, USA.
authors.forename: Okkyung
authors.initials: O
authors.lastname: Rho
authors.affiliation: Department of Chemistry, The University of Texas at Austin, Austin, TX, USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Camelio
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
authors.forename: Dionicio
authors.initials: D
authors.lastname: Siegel
authors.affiliation: Department of Pharmacology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Slaga
authors.affiliation: Division of Pharmacology and Toxicology in College of Pharmacy, The University of Texas at Austin, Austin, TX, USA.|Department of Nutritional Sciences, The University of Texas at Austin, Austin, TX, USA.
authors.forename: John
authors.initials: J
authors.lastname: DiGiovanni
mesh_terms: D000818:Animals; D004347:Drug Interactions; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D053978:Pentacyclic Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D031344:Perilla frutescens / Q000737:chemistry*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D053978:Pentacyclic Triterpenes; D010936:Plant Extracts; D013755:Tetradecanoylphorbol Acetate
keywords: P. frutescens; chemoprevention; pentacyclic triterpenes; skin tumor promotion; ursolic acid