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- Title
Gomisin N enhances TNF-α-induced apoptosis via inhibition of the NF-κB and EGFR survival pathways.
- Authors
Waiwut, Pornthip; Myoung-Sook Shin; Inujima, Akiko; Yue Zhou; Koizumi, Keiichi; Saiki, Ikuo; Sakurai, Hiroaki
- Abstract
Tumor necrosis factor (TNF-α) is a pleiotropic cytokine that plays an important role in the control of cell proliferation, differentiation, and apoptosis. TNF-α-induced apoptosis is limited by TAK1-mediated activation of NF-κB (mainly p65-p50 hetrodimer) signaling pathway. We have recently reported that TAK1 regulates phosphorylation of EGFR at Ser-1046/7 through p38 MAPK, which cooperates with NF-κB in TNF-α-induced apoptosis. The present study investigated the effect of gomisins A and N, dibenzocyclooctadiene lignans isolated from the fruit of Schisandra chinensis, on TNF-α-induced apoptosis in HeLa cells. Gomisins A and N strongly promoted TNF-α-induced cleavage of caspase-3 and PARP-1, which are key markers of apoptosis. We found that gomisin N, but not gomisin A, inhibited the TNF-α-induced activation of NF-κB by suppressing the activation of IKKα. Gomisin N also inhibited p38-mediated phosphorylation of the EGFR at Ser-1046/7 and subsequent endocytosis of EGFR, another prosurvival pathway. The findings suggested that gomisin N enhanced TNF-α-induced apoptosis by suppressing of NF-κB and EGFR signaling pathways.
- Subjects
APOPTOSIS; CELL death; SCHISANDRA chinensis; TUMOR necrosis factors; CYTOKINES
- Publication
Molecular & Cellular Biochemistry, 2011, Vol 350, Issue 1/2, p169
- ISSN
0300-8177
- Publication type
Article
- DOI
10.1007/s11010-010-0695-z