Related Experiment Video
Updated: Jun 2, 2026
![Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F60445.jpg&w=3840&q=50)
Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)
Published on: December 19, 2019
Antitumor-promoting activity of oligomeric proanthocyanidins in mouse epidermis in-vivo
1KANSAS STATE UNIV AGR & APPL SCI,DIV BIOL,ANTI-CANC DRUG LAB,ACKERT HALL,MANHATTAN,KS 66506. US FOREST SERV,SO FOREST EXPT STN,PINEVILLE,LA 71360.
Abstract:
The flavanoid catechin and heterogenous samples of oligomeric proanthocyanidins extracted from various sources were compared for their ability to inhibit the biochemical and biological effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) in mouse epidermis in vivo. Topical applications of catechin fail to alter the hydroperoxide response to TPA but inhibit the induction of ornithine decarboxylase (ODC) activity and, to a lesser degree, the stimulation of RNA, protein, and DNA synthesis caused by this tumor promoter. Under similar conditions, condensed tannins (CTs) from guamuchil, loblolly pine, and southern red oak barks inhibit to various degrees all these biochemical markers of TPA promotion. The most effective antioxidant, loblolly pine bark CT, also inhibits TPA-induced ODC activity and macromolecule synthesis to a much greater degree than catechin or the other CTs tested. Pecan nut pith CT, however, has no inhibitory activity in this system. Pretreatments with 4 and 12 mg of loblolly pine bark CT remarkably inhibit the incidence and yield of skin tumors promoted by TPA in initiated mice, whereas similar doses of catechin are ineffective. Loblolly pine bark CT inhibits the 2nd rather than the 1st stage of tumor promotion. In contrast to their monomer units, therefore, some naturally occurring polyflavanoids have antioxidant activities and may be valuable against tumor propagation but their efficacy may vary considerably depending on their origin and structure.
Insights
Certain polyflavanoids, like loblolly pine bark condensed tannins (CTs), show significant antioxidant activity and inhibit tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA) in mice, unlike catechin.
Area of Science:
- Natural product chemistry
- Cancer research
- Dermatology
Background:
- 12-O-tetradecanoylphorbol-13-acetate (TPA) is a tumor promoter that induces biochemical and biological changes in mouse epidermis.
- Flavonoids, such as catechin, and oligomeric proanthocyanidins (polyflavanoids) are plant-derived compounds with potential biological activities.
Purpose of the Study:
- To compare the inhibitory effects of catechin and various condensed tannins (CTs) on TPA-induced effects in mouse epidermis.
- To evaluate the efficacy of these compounds in preventing TPA-promoted skin tumors in vivo.
Main Methods:
- In vivo studies using mouse epidermis treated with TPA.
- Measurement of biochemical markers: hydroperoxide response, ornithine decarboxylase (ODC) activity, and synthesis of RNA, protein, and DNA.
- Assessment of tumor incidence and yield after topical application of TPA and test compounds.
Main Results:
- Catechin did not affect the hydroperoxide response but partially inhibited TPA-induced ODC activity and macromolecule synthesis.
- Condensed tannins from guamuchil, loblolly pine, and southern red oak barks inhibited various TPA-induced biochemical markers.
- Loblolly pine bark CT was the most potent inhibitor, significantly reducing TPA-induced ODC activity, macromolecule synthesis, and skin tumor promotion.
- Catechin was ineffective in preventing TPA-promoted skin tumors, while loblolly pine bark CT demonstrated significant efficacy, particularly in the second stage of tumor promotion.
Conclusions:
- Some naturally occurring polyflavanoids, specifically certain CTs, possess antioxidant and anti-tumor promoting activities.
- The efficacy of these compounds varies significantly based on their origin and structure.
- Loblolly pine bark CT shows promise as a chemopreventive agent against TPA-promoted skin tumors.
