Evaluation of pentacyclic triterpenes found in Perilla frutescens for inhibition of skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate

Oncotarget. 2015 Nov 17;6(36):39292-306. doi: 10.18632/oncotarget.5751.


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.

Keywords: P. frutescens; chemoprevention; pentacyclic triterpenes; skin tumor promotion; ursolic acid.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Interactions
  • Female
  • Mice
  • Mice, Inbred ICR
  • Pentacyclic Triterpenes / isolation & purification
  • Pentacyclic Triterpenes / pharmacology*
  • Perilla frutescens / chemistry*
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology
  • Signal Transduction
  • Skin Neoplasms / chemically induced*
  • Skin Neoplasms / pathology
  • Skin Neoplasms / prevention & control*
  • Tetradecanoylphorbol Acetate / pharmacology*


  • Pentacyclic Triterpenes
  • Plant Extracts
  • Tetradecanoylphorbol Acetate