Anti-cancer effect of naringenin chalcone is mediated via the induction of autophagy, apoptosis and activation of PI3K/Akt signalling pathway

Shuai Zhang,Zong-Fei Jiang,Chun-Yu Song,Qiang Pan,Wen-Hua Zhang

doi:10.3329/bjp.v11i3.27518

Abstract

The aim of the current study was to investigate the in vitro and in vivo anti-tumor effects of naringenin chalcone in U87MG human glioblastoma cells and in xenograft mice model. The effect of naringenin chalcone on apoptosis induction was assessed by fluorescence microscopy using acridine orange/ethidium bromide and Hoechst 33342. Effect of the compound on PI3K/Akt signalling proteins was assessed by Western blot assay. Naringenin chalcone induced dose-dependent as well as time-dependent cytotoxic effects in these cells. Transmission electron microscopy showed that naringenin chalcone induced the formation of autophagic vacuoles. The number and size of these autophagic vacuoles increased with increasing dose of naringenin chalcone. It also led to the activation of both phosphorylated as well as non-phosphorylated PI3K and Akt proteins. In vivo results showed that both tumor volume and tumor weight were lesser in naringenin chalcone-treated groups with its different doses than in vehicle control group.Video Clip<a href="https://youtube.com/v/Av2CQPTj1Yg">Cell proliferation assay:</a> 1 min 08 sec

Highlights

Malignant gliomas are the primary brain cancers accounting for about 80% of the all cancers targeting central nervous system
Acridine orange/ethidium bromide (AO/ETBR) and Hoechst 33342 were purchased from Wuhan Boster Biological Technology Ltd. (China)
The in vitro and in vivo anti-tumor effects of naringenin chalcone were evaluated against U87MG human glioblastoma cells using MTT assay

Summary

Introduction

Malignant gliomas are the primary brain cancers accounting for about 80% of the all cancers targeting central nervous system. The incompetence of many chemotherapeutic drugs to cross the blood-brain barrier is the principal reason of the limitations of chemotherapy in the treatment of human gliomas. This is the reason that there are very few active drugs available for its treatment. As such there is a pressing need for the design and development of novel and promising anti-glioma chemotherapeutic agents (Das et al, 2010)

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