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
The grapefruit osthole act as a natural inhibitor of HDACs.
Osthole inhibited the growth of A549 cells, in a time- and concentration-dependent manner.
Ostholeinduced apoptosis and the caspase-9 was also increased by osthole treatment.
The reaction of (1,3-diphenyl-1H-pyrazole-4-carbaldehyde) with different aromatic amines and triethylphosphite in the presence of magnesium perchlorate as a catalyst resulted in high yields of new α-aminophosphonates containing pyrazole moiety. The structures of the newly prepared α-aminophosphonates were confirmed using IR, elemental analysis, 1 H NMR, and 13 C NMR spectra. The antibacterial analysis of the prepared compounds showed potential inhibitory effects against the selected bacterial strains with minimal inhibitory concentrations (MIC) ranging from 12.5 to 3.125 mg/mL compared to the start compound. Some compounds have exhibited higher DPPH scavenging activity. Further, the molecular docking studies illustrated that the synthesized compounds have an inhibitory effect against topoisomerase II, which targets many approved drugs. The best modified α-aminophosphonates compound had the highest binding affinity, with a value of À 7.57 kcal/mol. Modified α-aminophosphonates can be employed as a feasible starting point for generating new antimicrobial and anticancer agents and incorporating new reducing agents into therapeutic formulations.
Among seven homologs of cytochrome b561 in a model organism C. elegans, Cecytb-2 was confirmed to be expressed in digestive organs and was considered as a homolog of human Dcytb functioning as a ferric reductase. Cecytb-2 protein was expressed in Pichia pastoris cells, purified, and reconstituted into a phospholipid bilayer nanodisc. The reconstituted Cecytb-2 in nanodisc environments was extremely stable and more reducible with ascorbate than in a detergent-micelle state. We confirmed the ferric reductase activity of Cecytb-2 by analyzing the oxidation of ferrous heme upon addition of ferric substrate under anaerobic conditions, where clear and saturable dependencies on the substrate concentrations following the Michaelis–Menten equation were observed. Further, we confirmed that the ferric substrate was converted to a ferrous state by using a nitroso-PSAP assay. Importantly, we observed that the ferric reductase activity of Cecytb-2 became enhanced in the phospholipid bilayer nanodisc.
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