Santin (5,7-Dihydroxy-3,6,4′-Trimetoxy-Flavone) Enhances TRAIL-Mediated Apoptosis in Colon Cancer Cells

TRAIL (Tumor necrosis factor-Related Apoptosis-Inducing Ligand) has the ability to selectively kill cancer cells without being toxic to normal cells. This endogenous ligand plays an important role in surveillance and anti-tumor immunity. However, numerous tumor cells are resistant to TRAIL-induced apoptosis. In this study, the apoptotic effect of santin in combination with TRAIL on colon cancer cells was examined. Flow cytometry was used to detect the apoptosis and expression of death receptors (TRAIL-R1/DR4 and TRAIL-R2/DR5). Mitochondrial membrane potential (Delta psi m) was evaluated by DePsipher staining with the use of fluorescence microscopy. We have shown for the first time that flavonoid santin synergizes with TRAIL to induce apoptosis in colon cancer cells. Santin induced TRAIL-mediated apoptosis through increased expression of death receptors TRAIL-R1 and TRAIL-R2 and augmented disruption of the mitochondrial membrane in SW480 and SW620 cancer cells. The obtained data may indicate the potential role of santin in colon cancer chemoprevention through the enhancement of TRAIL-mediated apoptosis.

Automated summary

This study examined the apoptotic effect of santin in combination with TRAIL on colon cancer cells. Flow cytometry and fluorescence microscopy were used to observe apoptosis and death receptor expression. It was found that santin synergized with TRAIL to induce apoptosis in colon cancer cells. This synergistic effect was achieved by increasing the expression of death receptors TRAIL-R1 and TRAIL-R2 and altering the mitochondrial membrane potential.