Antitumor Activity of Elaeocarpus ganitrus (Rudraksha) Bead Extract Mediated Silver Nanoparticles in Preclinical Models
摘要
The present study aims to evaluate the cytotoxic and anti-tumor activity of Eleaocarpus ganitrus (Rudraksha) bead extract mediated silver nanoparticles (REMAG) in preclinical models. The in vitro cytotoxic activity was tested on CT26, HCT116, NSCLC-A549, FaDu, and MCF7 cancer cell lines. The apoptotic potential of REMAG was evaluated in HCT116 cell line where maximum cytotoxic response was obtained. The in vivo anti-tumor efficacy of REMAG was assessed in CT26 syngeneic tumor model and HCT116 xenograft tumor model. In vitro studies revealed a significant dose-dependent cytotoxic effect of REMAG with an IC50 of 16.9 ± 1.5 µg/mL (FaDu), 5.7 ± 0.1 µg/mL (A549), 3.4 ± 0.01 µg/mL (CT26), 3.9 ± 0.03 µg/mL (HCT116) and 4.0 ± 0.01 µg/mL (MCF7) µg/mL. Protein expression analysis of apoptotic markers showed an increase in 7.94-, 2.93-, and 4.87-fold expression of caspase-3 cleaved caspases-3 and Bax, respectively, suggesting the apoptosis promotion activity of REMAG. Treatment of REMAG (50 mg/kg, Q2Dx8) demonstrated significant tumor growth inhibition (%TGI) of 55% on day 15 in syngeneic CT26 mice model in contrast to vehicle treated group (p < 0.001). Further, REMAG treatment significantly lowered the tumor volume in HCT116 xenograft study in a dose-dependent manner with a tumor volume of 911 ± 211 mm3 (5 mg/kg); 370 ± 139 mm3 (15 mg/kg); and 273 ± 47 mm3 (30 mg/kg) as compared to vehicle treated group (1557 ± 98 mm3) (p < 0.05). Rudraksha bead extract mediated silver nanoparticles may serve as promising environmentally sustainable anti-cancer therapeutic modality warranting further research for bench to bedside translation.