Annona muricata silver nanoparticles exhibit strong anticancer activities against cervical and prostate adenocarcinomas through regulation of CASP9 and the CXCL1/CXCR2 genes axis
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Date
2021
Journal Title
Journal ISSN
Volume Title
Publisher
Tumor Biology
Abstract
Green synthesized nanoparticles have been earmarked for use in nanomedicine including for the development
of better anticancer drugs.
OBJECTIVE: The aim of this study was to undertake biochemical evaluation of anticancer activities of green synthesized
silver nanoparticles (AgNPs) from ethanolic extracts of fruits (AgNPs-F) and leaves (AgNPs-L) of Annona muricata.
METHODS:Previously synthesized silver nanoparticles were used for the study. The effects of the AgNPs and 5-Fluorouracil
were studied on PC3, HeLa and PNT1A cells. The resazurin, migration and colonogenic assays as well as qRT-PCR were
employed.
RESULTS: The AgNPs-F displayed significant antiproliferative effects against HeLa cells with an IC50 of 38.58 g/ml and
PC3 cells with an IC50 of 48.17 g/ml but selectively spared normal PNT1A cells (selectivity index of 7.8), in comparison
with first line drug 5FU and AgNPs-L whose selectivity index were 3.56 and 2.26 respectively. The migration assay revealed
potential inhibition of the metastatic activity of the cells by the AgNPs-F while the colonogenic assay indicated the permanent
effect of the AgNPs-F on the cancer cells yet being reversible on the normal cells in contrast with 5FU and AgNPs-L. CASP9
was significantly over expressed in all HeLa cells treated with the AgNPs-F (1.53-fold), AgNPs-L (1.52-fold) and 5FU
(4.30-fold). CXCL1 was under expressed in HeLa cells treated with AgNPs-F (0.69-fold) and AgNPs-L (0.58-fold) and over
expressed in cells treated with 5FU (4.95-fold), but the difference was not statistically significant. CXCR2 was significantly over expressed in HeLa cells treated with 5FU (8.66-fold) and AgNPs-F (1.12-fold) but under expressed in cells treated with
AgNPs-L (0.76-fold).
CONCLUSIONS: Here we show that biosynthesized AgNPs especially AgNPs-F can be used in the development of novel
and better anticancer drugs. The mechanism of action of the AgNPs involves activation of the intrinsic apoptosis pathway
through upregulation of CASP9 and concerted down regulation of the CXCL1/ CXCR2 gene axis.
Description
Keywords
Silver nanoparticles, HeLa, PC3, PNT1A, CASP9, CXCL1/CXCR2
Citation
Gavamukulya, Y., Maina, E. N., El-Shemy, H. A., Meroka, A. M., Kangogo, G. K., Magoma, G., & Wamunyokoli, F. (2021). Annona muricata silver nanoparticles exhibit strong anticancer activities against cervical and prostate adenocarcinomas through regulation of CASP9 and the CXCL1/CXCR2 genes axis. Tumor Biology, 43(1), 37-55. DOI:10.3233/TUB-200058