Molecular and Cellular Biochemistry

, Volume 350, Issue 1–2, pp 169–175 | Cite as

Gomisin N enhances TNF-α-induced apoptosis via inhibition of the NF-κB and EGFR survival pathways

  • Pornthip Waiwut
  • Myoung-Sook Shin
  • Akiko Inujima
  • Yue Zhou
  • Keiichi Koizumi
  • Ikuo Saiki
  • Hiroaki Sakurai


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.


TNF-α NF-κB EGFR Apoptosis Gomisin Schisandra chinensis 



This work was supported in part by Grants-in-Aid for Challenging Exploratory Research (No. 09002374) and for the Knowledge Custer Initiative Toyama/Ishikawa Region (Hokuriku Innovation Cluster for Health Science) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan, and a grant from the First Bank of Toyama Foundation.


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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Pornthip Waiwut
    • 1
  • Myoung-Sook Shin
    • 1
  • Akiko Inujima
    • 1
  • Yue Zhou
    • 1
  • Keiichi Koizumi
    • 1
  • Ikuo Saiki
    • 1
  • Hiroaki Sakurai
    • 1
  1. 1.Division of Pathogenic Biochemistry, Institute of Natural MedicineUniversity of ToyamaToyamaJapan

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