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. roseus
AgNPs 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. roseus
AgNPs on HepG2 was 4.38 ± 1.59 μg/mL while on THLE3 cells was 800 ± 1.55 μg/mL. Transcriptome profiling revealed an alteration of 296 genes.
C. roseus
AgNPs 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 clathrin-independent 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. roseus
AgNPs as an ideal anticancer candidate.