Effect of Apigenin on Notch signalingpathway in colorectal cancer cells: Deltex۱ and Hey۱ geneexpression

Introduction: Colorectal cancer is the second leading causeof cancer death in the world. Apigenin is a natural flavonoidthat has been shown to have several antitumor effects on cancercells, such as: induction of ROS production, induction of apoptosis,necroptosis and cellular autophagy, suppression of cellcycle, suppression of migration and cell invasion, stimulationof immune response and inhibition of Self-renewal characteristicsof cancer stem cells. Notch signaling pathway is involvedin cell proliferation, differentiation, self-renewal and survivalin colorectal cells. In this study, we investigated the effect ofApigenin on the Notch signaling pathway in colorectal cells.Methods: Apigenin cytotoxicity was assessed by MTT assayand IC۵۰ obtained, then one concentration was selected. Cancercells (HT-۲۹) were treated with selected concentration (controlwithout treat). Primers were designed and synthesized. RNAextraction and cDNA synthesis were done and the expressionof Deltex۱ and Hey۱ genes from Notch signaling pathway weremeasured by real-time PCR. ROS was measured before and aftertreatment. Flow cytometry was used to investigate the effectof Apigenin on cell cycle and cell surface markers. Scratch assaywas used to measure cell migration, and Annexin V/PI wasused to check apoptosis.Results: According to the MTT assay, Apigenin had no significanteffect on the lethality of colorectal cancer cells in ۲۴ hoursand the highest level of lethality of cells was seen in ۷۲ hours.Our studies showed that Apigenin can affect Notch signalingpathway in colorectal cancer cells by changing Deltex۱ andHey۱ genes expression. Apigenin influenced ROS productionand migration in colorectal cancer cells. In addition, it affectedcell cycle and cell surface markers.Conclusion: Considering that Apigenin can affect the Notchsignaling pathway involved in colorectal cancer, Apigenin canbe used as a therapeutic strategy to alleviate colorectal cancerseverity.

کلیدواژه ها:

Colorectal cancer ، Apigenin ، Notch ، ROS