Neoalbaconol induces cell death through necroptosis by regulating RIPK-dependent autocrine TNFα and ROS production

Xinfang Yu, Qipan Deng, Wei Li, Lanbo Xiao, Xiangjian Luo, Xiaolan Liu, Lifang Yang, Songling Peng, Zhihui Ding, Tao Feng, Jian Zhou, Jia Fan, Ann M. Bode, Zigang Dong, Jikai Liu, Ya Cao

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Necroptosis/regulated necrosis is a caspase-independent, but receptor interacting protein kinase (RIPK)-dependent form of cell death. In previous studies, neoalbaconol (NA), a constituent extracted from Albatrellus confluens, was demonstrated to induce necroptosis in some cancer cell lines. The molecular mechanism of NA-induced necroptosis is described in this research study. We determined that NA-induced cell death is partly dependent on tumor necrosis factor a (TNFα) feed-forward signaling. More importantly, NA abolished the ubiquitination of RIPK1 by down-regulating E3 ubiquitin ligases, cellular inhibitors of apoptosis protein 1/2 (cIAP1/2) and TNFα receptor-associated factors (TRAFs). The suppression of RIPK1 ubiquitination induced the activation of the non-canonical nuclear factor-κB (NF-κB) pathway and stimulated the transcription of TNFα. Moreover, we also found that NA caused RIPK3-mediated reactive oxygen species (ROS) production and contribution to cell death. Taken together, these results suggested that two distinct mechanisms are involved in NA-induced necroptosis and include RIPK1/NF-κB-dependent expression of TNFα and RIPK3-dependent generation of ROS.

Original languageEnglish (US)
Pages (from-to)1995-2008
Number of pages14
JournalOncotarget
Volume6
Issue number4
DOIs
StatePublished - 2015

Keywords

  • NF-κB Signaling pathway
  • Necoalbaconol
  • Necroptosis
  • RIPK
  • ROS
  • TNFα

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    Yu, X., Deng, Q., Li, W., Xiao, L., Luo, X., Liu, X., Yang, L., Peng, S., Ding, Z., Feng, T., Zhou, J., Fan, J., Bode, A. M., Dong, Z., Liu, J., & Cao, Y. (2015). Neoalbaconol induces cell death through necroptosis by regulating RIPK-dependent autocrine TNFα and ROS production. Oncotarget, 6(4), 1995-2008. https://doi.org/10.18632/oncotarget.3038