Annona muricata silver nanoparticles exhibit strong anticancer activities against cervical and prostate adenocarcinomas through regulation of CASP9 and the CXCL1/CXCR2 genes axis
| Autor: | Geoffrey K Kangogo, Hany A. El-Shemy, Fred Wamunyokoli, Yahaya Gavamukulya, Gabriel Magoma, Amos M. Meroka, Esther N. Maina |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Silver Cell Survival Chemokine CXCL1 Metal Nanoparticles Uterine Cervical Neoplasms Antineoplastic Agents Adenocarcinoma Annona Receptors Interleukin-8B Silver nanoparticle Cell Line HeLa 03 medical and health sciences 0302 clinical medicine Cell Movement medicine Humans CXC chemokine receptors IC50 Annona muricata Cell Proliferation Migration Assay biology Plant Extracts Chemistry Prostatic Neoplasms Green Chemistry Technology General Medicine biology.organism_classification Molecular biology Caspase 9 Gene Expression Regulation Neoplastic 030104 developmental biology Mechanism of action 030220 oncology & carcinogenesis Cancer cell Female medicine.symptom |
| Zdroj: | Tumor Biology. 43:37-55 |
| ISSN: | 1423-0380 1010-4283 |
| Popis: | BACKGROUND: 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 38.58μg/ml and PC3 cells with an IC50 of 48.17μg/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. |
| Databáze: | OpenAIRE |
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