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KMID : 0620720220280020080
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Natural Product Sciences
2022 Volume.28 No. 2 p.80 ~ p.95
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Anti-metastatic Effect of Natural Product-motivated Synthetic PPAR-γ Ligands
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Li Dan-Dan
Wang Ying
Ju Zhiran
Kim Eun-La
Hong Jong-Ki
Jung Jee-H.
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Abstract
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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.
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KEYWORD
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PPAR-γ agonists, anti-metastasis, epithelial-to-mesenchymal transition, colorectal cancer
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