Related Experiment Video
Updated: Oct 26, 2026
Mouse Model of Oleic Acid-Induced Acute Respiratory Distress Syndrome
Published on: June 2, 2022
Inhibitory effect of oleanolic acid on 12-O-tetradecanoylphorbol-13-acetate-induced gene expression in mouse skin
1Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Abstract:
Oleanolic acid (OA) has been shown to inhibit mouse skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA). This study was designed to examine the effect of OA on the TPA-induced expression of the ornithine decarboxylase (ODC) gene as well as other genes. OA inhibited the induction of ODC activity and mRNA level produced by TPA in the skin of female CD-1 mice. Preapplication of OA (10 mumol) to the mouse dorsal skin produced an approximately 50% decrease in TPA (8 nmol)-induced epidermal ODC activity, as well as ODC gene expression. These results suggest that OA inhibits TPA-induced ODC mainly at the transcriptional level. In addition to ODC, TPA also stimulated metallothionein (MT) gene expression in mouse skin. A dose of 2.5 mumol of OA diminished the TPA-induced MT mRNA 50%. Treatment with OA (10 mumol) after TPA (8 nmol) application also inhibited ODC and MT gene expression which suggests that OA does not compete with TPA for its receptor. OA pretreatment also prevented c-fos gene expression. All of these findings suggest that OA diminishes some signal transduction pathways of TPA to suppress target gene expression in mouse skin. This study suggests that OA might be a general inhibitor against TPA-stimulated gene expression in mouse skin.
Insights
Oleanolic acid (OA) significantly inhibits tumor promotion by TPA in mouse skin. It reduces TPA-induced gene expression of ornithine decarboxylase (ODC) and metallothionein (MT), suggesting OA is a general inhibitor of TPA-stimulated genes.
Area of Science:
- Pharmacology
- Molecular Biology
- Cancer Research
Background:
- Oleanolic acid (OA) is known to inhibit skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA).
- The precise molecular mechanisms underlying OA's inhibitory effects require further investigation.
Purpose of the Study:
- To investigate the impact of OA on TPA-induced gene expression, specifically focusing on ornithine decarboxylase (ODC) and other related genes.
- To elucidate the potential role of OA as an inhibitor of TPA-mediated signal transduction pathways.
Main Methods:
- CD-1 mice were treated with OA and/or TPA.
- Epidermal ODC activity and mRNA levels were measured.
- Gene expression of metallothionein (MT) and c-fos was analyzed via mRNA levels.
Main Results:
- OA pretreatment significantly reduced TPA-induced ODC activity and mRNA levels by approximately 50%.
- OA also inhibited TPA-induced metallothionein (MT) mRNA expression by 50%.
- OA administration post-TPA treatment inhibited ODC and MT gene expression, indicating it doesn't compete for the TPA receptor.
Conclusions:
- Oleanolic acid inhibits TPA-induced ODC expression primarily at the transcriptional level.
- OA appears to interfere with TPA-induced signal transduction pathways, suppressing target gene expression.
- OA demonstrates potential as a general inhibitor against TPA-stimulated gene expression in mouse skin.