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01-06-2020 | Original Article

Anticancer effects of brusatol in nasopharyngeal carcinoma through suppression of the Akt/mTOR signaling pathway

Authors: Songbin Guo, Jinling Zhang, Cairong Wei, Zhiyong Lu, Rulong Cai, Danqi Pan, Hanbin Zhang, Baoxia Liang, Zhenfeng Zhang

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2020

Abstract

Purpose

Brusatol, a natural quassinoid that is isolated from a traditional Chinese herbal medicine known as Bruceae Fructus, possesses biological activity in various types of human cancers, but its effects in nasopharyngeal carcinoma (NPC) have not been reported. This study aimed to explore the effect and molecular mechanism of brusatol in NPC in vivo and in vitro.

Methods

The antiproliferative effect of brusatol was assessed by MTT and colony formation assays. Apoptosis was determined by flow cytometry. The expression of mitochondrial apoptosis, cell cycle arrest, and Akt/mTOR pathway proteins were determined by western blot analysis. Further in vivo confirmation was performed in a nude mouse model.

Results

Brusatol showed antiproliferative activity against four human NPC cell lines (CNE-1, CNE-2, 5-8F, and 6-10B) in a dose-dependent manner. This antiproliferative effect was accompanied by mitochondrial apoptosis and cell cycle arrest through the modulation of several key molecular targets, such as Bcl-xl, Bcl-2, Bad, Bax, PARP, Caspase-9, Caspase-7, Caspase-3, Cdc25c, Cyclin B1, Cdc2 p34, and Cyclin D1. In addition, we found that brusatol inhibited the activation of Akt, mTOR, 4EBP1, and S6K, suggesting that the Akt/mTOR pathway is a key underlying mechanism by which brusatol inhibits growth and promotes apoptosis. Further in vivo nude mouse models proved that brusatol significantly inhibited the growth of CNE-1 xenografts with no significant toxicity.

Conclusions

These observations indicate that brusatol is a promising antitumor drug candidate or a supplement to current chemotherapeutic therapies to treat NPC.

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Title: Anticancer effects of brusatol in nasopharyngeal carcinoma through suppression of the Akt/mTOR signaling pathway
Authors: Songbin Guo
Jinling Zhang
Cairong Wei
Zhiyong Lu
Rulong Cai
Danqi Pan
Hanbin Zhang
Baoxia Liang
Zhenfeng Zhang
Publication date: 01-06-2020
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 6/2020
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-020-04083-3

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