Nat Prod Sci.  2022 Jun;28(2):80-88. 10.20307/nps.2022.28.2.80.

Anti-metastatic Effect of Natural Product-motivated Synthetic PPAR-γ Ligands

• Li Dd
• Wang Y
• Ju Z
• Kim EL
• Hong J
• Jung JH

• KMID: 2530936
• DOI: http://doi.org/10.20307/nps.2022.28.2.80

Abstract

Colorectal cancer is one of the most common cancers globally, ranking second for the number of cancer-related deaths. Metastasis has been reported as the main cause of death in patients with colorectal cancer. Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a transcription factor that functions as a tumor suppressor by inhibiting cellular proliferation, migration, and invasion. In our previous efforts to generate natural product-motivated PPAR-γ ligands, the compounds 1 and 2 were obtained. These compounds activated PPAR-γ and inhibited the migration and invasion of HCT116 colorectal cancer cells, and they were also found to inhibit the epithelial-to-mesenchymal transition, which is a key process in cancer metastasis. Compounds 1 and 2 upregulated expression of the epithelial marker (E-cadherin), and downregulated expression of the mesenchymal marker (N-cadherin) and transcriptional factor (Snail). Therefore, the PPAR-γ agonists 1 and 2 could serve as a valuable model for the study on anti-metastatic leads for the treatment of colorectal cancer.

Keyword

PPAR-γ agonists; anti-metastasis; epithelial-to-mesenchymal transition; colorectal cancer