Abstract
Introduction: Plant-mediated synthesis of silver nanoparticles (AgNPs) is accounted as an ecofriendly process. The present study was conducted to estimate the potency of biogenic AgNPs against Ehrlich ascites carcinoma (EAC) cells in vitro and EAC-bearing mice in vivo.
 Methods: AgNPs were prepared using mango leaves extract and characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), and transmission electron microscopy (TEM). Ehrlich ascites carcinoma (EAC) mouse model was established by intraperitoneal injection of 1 x 106 EAC cells. Biogenic AgNPs- alone or combined with Doxorubicin (DOX)- was administered intraperitoneally day by day for two weeks.
 Results: Biologically synthesized AgNPs showed a cytotoxic effect against cultured EAC cells but with less toxicity toward normal cells compared to DOX, which had strong cytotoxicity against both cells. Biogenic AgNPs alone or combined with DOX triggered the cytotoxicity against the EAC-bearing mouse model via decreasing body weight, tumor volume, and the number of viable tumor cells. The combined treatment (AgNPs-DOX) ameliorated the drastic effect induced by injection of EAC cells through improving liver and kidney functions compared to those treated with DOX alone. In addition, the combined treatment showed an elevation in the expression of Bax and caspase-3, and a reduction in the expression of Bcl-2 protein in the EAC cells. Furthermore, this combined treatment effectively arrested the cell cycle at the G0/G1 phase. Moreover, the combined treatment with AgNPs-DOX caused a significant reduction in the activity of ornithine decarboxylase (ODC).
 Conclusion: These findings suggest that biogenic AgNPs could be useful in developing a potent combination therapy against different types of cancers.
Highlights
Plant-mediated synthesis of silver nanoparticles (AgNPs) is accounted as an ecofriendly process
Biologically synthesized AgNPs showed a cytotoxic effect against cultured Ehrlich ascites carcinoma (EAC) cells but with less toxicity toward normal cells compared to DOX, which had strong cytotoxicity against both cells
The transmission electron microscopy (TEM) image (Figure 1 D) indicated that the sizes of AgNPs ranged from 9.12 to 20.95 nm, which were compatible with the results of our X-ray diffraction (XRD) measurements
Summary
Plant-mediated synthesis of silver nanoparticles (AgNPs) is accounted as an ecofriendly process. Biogenic AgNPs alone or combined with DOX triggered the cytotoxicity against the EAC-bearing mouse model via decreasing body weight, tumor volume, and the number of viable tumor cells. The combined treatment showed an elevation in the expression of Bax and caspase-3, and a reduction in the expression of Bcl-2 protein in the EAC cells. Metal nanoparticles have been found as the most promising targets of various scientific challenges due to their versatile applications in many fields, such as electronics, biomedical applications, materials science, and environmental remediation Among these metal nanoparticles, silver nanoparticles (AgNPs) are very unique due to their anti-microbial and anticancer activities 7. Silver nanoparticles can be prepared by various physical, chemical, and biological methods. AgNPs have been reported to have cytotoxicity against various cancer
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