Comparison of effects of P-coumaric acid and coumarin on colorectal cancer cell line by inducing apoptosis and autophagy

Abstract

Objective: Autophagy, as a cellular pathway involved inremoving damaged proteins and organelles, performs a vitalfunction in the homeostasis and fate of cells. Natural compoundsof coumarin (CO) are found in a variety of herbs. Due to theirmany medicinal properties, including antitumor and antiproliferative activity, they are involved in apoptosis and autophagyprocesses. This investigation desired to analyze the apoptotic andautophagic effects of p-coumaric acid (PCA) and CO on HT-29cells cultured in fibrin hydrogel.Materials and Methods: Cell viability and apoptotic andautophagic changes were evaluated by MTT assay, AcridineOrange, 4′,6-diamidino-2-phenylindole (DAPI), andmonodansylcadaverine (MDC) staining. The expression Bax, Bad,Bcl2, Lc3, Beclin-1, P53 and Atg5 was respectively measured byqRT-PCR and Western blotting.Results: CO (IC50=25 μM) and PCA (IC50=150 μM) had a doseand time-dependent cytotoxic effect in HT-29 cells. So, thecytotoxic effects of CO were significantly higher than PCA andthese differences were also evident in cell morphologyinvestigations. The data illustrated a high expression of proapoptotic and pro-autophagic genes and a declined expression ofanti-apoptotic and anti-autophagic genes.Conclusion: CO (that was more potent) and p-coumaric acidinduced autophagy via PI3K/Akt/mTOR and AMPK/mTORsignaling on HT-29 cells.

Keywords

• autophagy
• cancer phytotherapy
• coumarin
• signaling pathway