Piceatannol enhances TRAIL-induced apoptosis in human leukemia THP-1 cells - GreenMedInfo Summary
Piceatannol enhances TRAIL-induced apoptosis in human leukemia THP-1 cells through Sp1- and ERK-dependent DR5 up-regulation.
Toxicol In Vitro. 2011 Apr ;25(3):605-12. Epub 2010 Dec 15. PMID: 21167276
Although piceatannol (PIC) is known to mediate anti-cancer, anti-inflammatory, and anti-oxidant activities, little is known about the mechanism of PIC in terms of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. In this study, we examined whether combined treatment with PIC and TRAIL synergistically induces apoptosis in THP-1 leukemia cells. Results indicate that PIC substantially enhances TRAIL-induced cell death including DNA fragmentation and poly(ADP-ribose) polymerase cleavage. Consistent with TRAIL-induced apoptosis, PIC significantly increased the mRNA and protein expression levels of DR5, a death receptor of TRAIL. Further, PIC enhanced DR5 promoter activity via Sp1 activation. Interestingly, the DR5 chimera antibodies significantly suppressed PIC and TRAIL-mediated apoptosis. The inhibitor of ERK also decreased PIC and TRAIL-induced apoptosis by blocking DR5 expression. In conclusion, our results suggest that PIC sensitizes TRAIL-induced-apoptosis via Sp1- and ERK-dependent DR5 up-regulation.