A study on ER stress-induced apoptosis pathway in cervical cancer HeLa cells treated with biosynthesized gold nanoparticles

M R Kamala Priya,Priya R Iyer

doi:10.1186/s42269-021-00670-3

Abstract

BackgroundThe expression of apoptotic family of protein plays a major role in induction of programmed cell death. There are six major apoptotic proteins such as Caspase 12, Bcl 2, BAX, Cytochrome c, PARP3 and Mcl1. All these proteins have crucial role in the regulation of apoptosis through mitochondrial degradation, DNA damage, nuclear condensation and eventually cell death of the cancerous cells. It was observed that the apoptotic pathway has been initiated in the cancer cells from the expression of the apoptotic proteins. The results emphasized that the apoptotic cell death has been induced by the nanomaterials against cervical cancer HeLa cell line.MethodsInitially, the nanomaterials were individually checked for potential anticancer activities through MTT assay. The cervical cancer HeLa cell line was treated with nanoparticles, nanoconjugates, nano-dox conjugate and chitosan–nano-dox conjugates. The cell lysates were processed for SDS–PAGE followed by Western blotting. The apoptotic expression has been studied for six major apoptotic proteins such as Caspase 12, Bcl 2, BAX, Cytochrome c, PARP3 and Mcl 1.ResultsIn the present study, the biosynthesized gold nanoparticles, nanoconjugates, nano-dox conjugate, chitosan–nano-dox conjugate were treated against cervical cancer HeLa cell line. The results demonstrated anticancer effects of the nanocompounds implying nanoparticles induced apoptotic pathway in the cancer cells. Further apoptotic expression was studied for six major apoptotic proteins such as Caspase 12, Bcl 2, BAX, Cytochrome c, PARP3 and Mcl 1. The present study was focussed on anticancer efficiency of biosynthesized nanomaterials.ConclusionsThe in vitro anticancer study showed that the nanomaterials induced cell death over the treated cervical cancer cells. In the process of apoptotic cell death, the caspase cascade pathway was activated. The gene expression was checked in line with some of the genes involved in apoptosis, cell death. The expression was checked for Caspase 12, BAX, Bcl2, cyt c, PARP3 and Mcl 1. The expression of apoptotic proteins suggested that the cancer cell death was mediated through ER stress-induced pathway involving the major apoptotic proteins.

Highlights

The expression of apoptotic family of protein plays a major role in induction of programmed cell death
In order to increase the bioavailability in a sustained release manner, the drug was conjugated with the synthesized nanoparticles and chitosan through STPP-mediated homogenization The expression of apoptotic proteins suggested that the cancer cell death was mediated through ER stress-induced pathway involving the major apoptotic proteins such as Caspase 12, BAX, Bcl2, Cytochrome c, PARP3 and Mcl1
The biosynthesized gold nanoparticles, nanoconjugates, nano-dox conjugate, chitosan–nano-dox conjugate were treated against cervical cancer HeLa cell line

Summary

Introduction

The expression of apoptotic family of protein plays a major role in induction of programmed cell death. There are six major apoptotic proteins such as Caspase 12, Bcl 2, BAX, Cytochrome c, PARP3 and Mcl. There are six major apoptotic proteins such as Caspase 12, Bcl 2, BAX, Cytochrome c, PARP3 and Mcl1 All these proteins have crucial role in the regulation of apoptosis through mitochondrial degradation, DNA damage, nuclear condensation and eventually cell death of the cancerous cells. The reactions lead to the induction of apoptotic pathway in the cells either through intrinsic pathway or extrinsic pathway by p53 activation. Bcl-2 family of proteins play the central role in regulation of apoptosis. Bcl-xS promotes apoptosis by caspase and BH3-dependent cascade leading to release of Cytochrome c. Bak and BAX proteins play an important role in the caspase cascade (http://atlasgeneticsoncology.org/Genes/GC_BCL2L1.html)

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