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Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
Published on: September 13, 2018
Tetrandrine induces apoptosis in human neuroblastoma through regulating the Hippo/YAP signaling pathway
Qian Zhao1, Xi Jia2, Yuanyuan Zhang3
1Department of Otolaryngology, The First Affiliated Hospital, Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, Shaanxi, China.
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.
Insights
Tetrandrine (TET) inhibits neuroblastoma (NB) growth and triggers cell death. Its anti-cancer effects involve reducing Bcl-2 via the Hippo/YAP pathway, offering a potential therapeutic strategy for NB.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Tetrandrine (TET), a natural alkaloid, exhibits anti-cancer properties against various tumors.
- The precise mechanism of TET's anti-cancer activity, particularly in neuroblastoma (NB), is not fully understood.
Purpose of the Study:
- To investigate the anti-cancer effects of TET on neuroblastoma (NB) cells.
- To elucidate the molecular mechanisms underlying TET's efficacy, focusing on apoptosis and the Hippo/YAP pathway.
Main Methods:
- In vitro and in vivo experiments were conducted using neuroblastoma models.
- Analysis included cell proliferation assays, apoptosis detection, and Western blotting to assess protein expression (Bcl-2, YAP).
- YAP overexpression was used to evaluate its role in TET's mechanism.
Main Results:
- TET significantly inhibited NB cell proliferation and induced apoptosis both in vitro and in vivo.
- TET treatment led to decreased expression of the anti-apoptotic protein Bcl-2.
- The Hippo/YAP pathway was identified as a key regulator in the down-regulation of Bcl-2 by TET.
- Overexpression of YAP partially reversed the anti-proliferative and pro-apoptotic effects of TET.
Conclusions:
- Tetrandrine demonstrates significant anti-cancer potential against neuroblastoma.
- The anti-tumor activity of TET is mediated through the inhibition of Bcl-2 expression via the Hippo/YAP pathway.
- Targeting the Hippo/YAP pathway presents a promising therapeutic avenue for neuroblastoma treatment.
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