Tetrandrine induces apoptosis in human neuroblastoma through regulating the Hippo/YAP signaling pathway

Biochem Biophys Res Commun. 2019 Jun 11;513(4):846-851. doi: 10.1016/j.bbrc.2019.04.075. Epub 2019 Apr 16.

Abstract

Tetrandrine (TET), a bis-benzylisoquinoline alkaloid, shows cytotoxicity against several different types of tumors. However, the mechanism by which TET exerts its anti-cancer capabilities remains unclear. In this study, we confirmed that TET inhibits proliferation and induces apoptosis in neuroblastoma (NB) in vitro and in vivo. Moreover, we revealed that the anti-cancer ability of TET is associated with a decreased expression of anti-apoptotic Bcl-2. Importantly, we demonstrated that the Hippo/YAP pathway is involved in down-regulating of Bcl-2. Notably, YAP overexpression promoted proliferation and suppressed apoptosis, even partially reversed TET-induced effects in NB cells. Our findings support the prospect that TET could be a potential therapeutic agent for NB, and suggest that targeting the Hippo/YAP pathway may represent a valuable approach to NB treatment.

Keywords: Apoptosis; Hippo/YAP signaling pathway; Neuroblastoma (NB); Tetrandrine (TET).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Apoptosis / drug effects*
  • Benzylisoquinolines / pharmacology*
  • Cell Proliferation / drug effects
  • Hippo Signaling Pathway
  • Humans
  • Neuroblastoma / drug therapy*
  • Neuroblastoma / pathology
  • Protein Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction
  • Transcription Factors / metabolism*
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • BCL2 protein, human
  • Benzylisoquinolines
  • Proto-Oncogene Proteins c-bcl-2
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • tetrandrine
  • Protein Serine-Threonine Kinases