Astragalin flavonoid inhibits proliferation in human lung carcinoma cells mediated via induction of caspase-dependent intrinsic pathway, ROS production, cell migration and invasion inhibition and targeting JAK/STAT signalling pathway.

Guoxing Xu,Rujuan Wang,Jie Jiang,Fangjing Wen,Xiaowu Shi,Biqing Yu

doi:10.14715/cmb/2021.67.2.7

Guoxing Xu, Rujuan Wang + Show 4 more

Open Access

https://doi.org/10.14715/cmb/2021.67.2.7

Copy DOI

Abstract

The aim of the current study was to investigate the anti-lung cancer effects of astragalin. Studies were also undertaken to evaluate its effects on apoptosis induction, ROS production, cellular migration and invasion and JAK/STAT3 signalling pathway. MTT assay was used to evaluate cell viability in NSCLC A549 cells after exposure to astragalin molecule. Apoptosis was investigated using AO/EB staining, comet assay and western blotting assay. Fluorescence microscopy was implemented to estimate ROS production. Cell migration and invasion were measured using transwell chambers assay. Effects of astragalin on JAK/STAT pathway were investigated using western blotting assay. Results showed astragalin molecule induced inhibition of proliferation in A549 cells in a dose-dependent fashion. Further, the antiproliferative effects were found to mediate via apoptosis as suggested by AO/EB staining and western blotting assay. Astragalin modulated the expressions of caspase-3, caspase-9, Bax, Bak, Cyt-c Bcl-2, XIAP and Bcl-xL. Astragalin induced DNA damage in A549 cells which too indicated apoptotic cell death. Astragalin molecule enhanced the production of ROS by A549 cells. It inhibited both cell migration and invasion of A549 cells in a concentration-dependent manner. Finally, astragalin drug was observed with remarkable potential of targeting JAK/STAT pathway in A549 NSCLC cells. These results indicated that astragalin drug could prove helpful in lung cancer treatment and research provided more in-vivo studies are performed.

Highlights

Natural products, a fathomless pool of biologically active chemical species, continue as leading and infinite resource in the field of drug discovery (1)
These results indicated that astragalin drug could prove helpful in lung cancer treatment and research provided more in-vivo studies are performed
Post A549 cells were exposed to variant concentration of astragalin (0150 μM), the cellular viability reduced considerably from 100% to nearly 15% (Fig. 1B)

Summary

Introduction

A fathomless pool of biologically active chemical species, continue as leading and infinite resource in the field of drug discovery (1). Flavonoids are a class of low molecular weight active natural product polyphenols showing remarkable structural diversity and molecules that are analogous to biological systems. This class of compounds has been identified with substantial pharmacological and biological activities including antiviral, anti-allergic, anti-inflammatory, anti-diabetic and anticancer activities (4,5). Astragalin has been shown with proapoptotic and proautophagic against several human cancer cell lines (17,18) This current study was designed to evaluate the anticancer effects with underlying mechanism of action of astragalin molecule against lung cancer

Objectives

Methods

Results

Conclusion