Evaluation of pentacyclic triterpenes found in Perilla frutescens for inhibition of skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate
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Jiyoon Cho1, Lisa Tremmel1, Okkyung Rho1, Andrew M. Camelio3, Dionicio Siegel4, Thomas J. Slaga5, John DiGiovanni1,2
1Division of Pharmacology and Toxicology in College of Pharmacy, The University of Texas at Austin, Austin, TX, USA
2Department of Nutritional Sciences, The University of Texas at Austin, Austin, TX, USA
3Department of Chemistry, The University of Texas at Austin, Austin, TX, USA
4Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA
5Department of Pharmacology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
John DiGiovanni, e-mail: [email protected]
Keywords: pentacyclic triterpenes, ursolic acid, P. frutescens, chemoprevention, skin tumor promotion
Received: August 13, 2015 Accepted: October 05, 2015 Published: October 15, 2015
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.
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