mRNA transcriptome profiling of human hepatocellular carcinoma cells HepG2 treated with Catharanthus roseus-silver nanoparticles  

作　　者：Nur Asna Azhar Siti Aishah Abu Bakar Marimuthu Citartan Nor Hazwani Ahmad 

机构地区：[1]Department of Biomedical Science,Advanced Medical and Dental Institute,Universiti Sains Malaysia,Kepala Batas 13200,Pulau Pinang,Malaysia [2]Liver Malignancies Research Program,Advanced Medical and Dental Institute,Universiti Sains Malaysia,Kepala Batas 13200,Pulau Pinang,Malaysia [3]Faculty of Bioresources and Food Industry,Universiti Sultan Zainal Abidin,Besut Campus,Besut 22200,Terengganu,Malaysia

出　　处：《World Journal of Hepatology》2023年第3期393-409,共17页世界肝病学杂志（英文版）（电子版）

基　　金：Fundamental Research Grant Scheme from the Malaysian Ministry of Higher Education,No.FRGS/1/2015/SG03/USM/03/1。

摘　　要：BACKGROUND The demand for the development of cancer nanomedicine has increased due to its great therapeutic value that can overcome the limitations of conventional cancer therapy.However,the presence of various bioactive compounds in crude plant extracts used for the synthesis of silver nanoparticles(AgNPs)makes its precise mechanisms of action unclear.AIM To assessed the mRNA transcriptome profiling of human HepG2 cells exposed to Catharanthus roseus G.Don(C.roseus)-AgNPs.METHODS The proliferative activity of hepatocellular carcinoma(HepG2)and normal human liver(THLE3)cells treated with C.roseusAgNPs were measured using MTT assay.The RNA samples were extracted and sequenced using BGIseq500 platform.This is followed by data filtering,mapping,gene expression analysis,differentially expression genes analysis,Gene Ontology analysis,and pathway analysis.RESULTS The mean IC 50 values of C.roseusAgNPs on HepG2 was 4.38±1.59μg/mL while on THLE3 cells was 800±1.55μg/mL.Transcriptome profiling revealed an alteration of 296 genes.C.roseusAgNPs induced the expression of stress-associated genes such as MT,HSP and HMOX-1.Cellular signalling pathways were potentially activated through MAPK,TNF and TGF pathways that are responsible for apoptosis and cell cycle arrest.The alteration of ARF6,EHD2,FGFR3,RhoA,EEA1,VPS28,VPS25,and TSG101 indicated the uptake of C.roseus-AgNPs via both clathrin-dependent and clathrinindependent endocytosis.CONCLUSION This study provides new insights into gene expression study of biosynthesised AgNPs on cancer cells.The cytotoxicity effect is mediated by the aberrant gene alteration,and more interestingly the unique selective antiproliferative properties indicate the C.roseusAgNPs as an ideal anticancer candidate.

关 键 词：Catharanthus roseus HEPG2 Silver nanoparticles TRANSCRIPTOME oxidative stress Apoptosis Cell cycle 

分 类 号：R285[医药卫生—中药学]