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.
Highlights
According to the American Cancer Society, there will be an estimated 1,658,370 new cancer cases diagnosed and 588,430 cancer deaths in the US in 2015
We examined the effect of 7 different triterpenes including ursolic acid (UA), oleanolic acid (OA), augustic acid (AA), corosolic acid (CA), 3-epi-corosolic acid (3-epiCA), maslinic acid (MA), and 3-epi-maslinic acid (3-epiMA) present in P. frutescens on epidermal proliferation, skin inflammation, inflammatory gene expression and epidermal signaling pathways induced by TPA
Analysis of epidermal signaling pathways induced by TPA revealed that there were variable effects of the different compounds on individual signaling pathways
Summary
According to the American Cancer Society, there will be an estimated 1,658,370 new cancer cases diagnosed and 588,430 cancer deaths in the US in 2015. In the mid-1970s, Michael Sporn created the term ‘chemoprevention’, which is defined as the use of natural or synthetic agents to reverse, inhibit or slow the process of carcinogenesis [2]. Various tumor models have been used to evaluate cancer preventive agents. The multi-stage skin carcinogenesis model is a well-established model of epithelial carcinogenesis with distinct and definable stages of tumor development [4, 5]. This model can be used to evaluate cancer chemopreventive agents on each individual stage of the carcinogenesis process and is useful for identifying potential mechanisms of chemopreventive action
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