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Synergistic anti-colon cancer effect of glycyrol and butyrate is associated with the enhanced activation of caspase-3 and structural features of glycyrol

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Coumarin-based anti-cancer agents have attracted considerable attention recently. Butyrate, a major short-chain fatty acid produced in colon by gut microbiota, has been shown to exert anticancer activity both in vitro and in vivo. In this study, we evaluated the anti-cancer effect of combining glycyrol (GC), a representative of coumarin compounds in licorice, or its analogues Glycycoumarin/Demethylsuberosin/Coumestrol (GCM/De/Coum) with butyrate in HT29 and HCT116 cells, and explored the relationship between the combined anti-cancer effect and structural features of coumarin compounds. Results showed the strongest inhibitory effect on cancer cells was induced by GC/butyrate combination via enhanced activation of caspase-3. Our data indicated the benzofuranyl, isopentenyl and methoxy groups presented in GC played critical role in its anti-cancer activity, while the furan group led to the further enhancement. The findings of the present study will be beneficial for developing coumarin-based compounds and coumarin compound-based regimen to fight against colon cancer.