Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5863136 | Toxicology in Vitro | 2011 | 8 Pages |
Abstract
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.
Keywords
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Authors
Chang-Hee Kang, Dong-Oh Moon, Yung Hyun Choi, Il-Whan Choi, Sung-Kwon Moon, Wun-Jae Kim, Gi-Young Kim,