Anticancer activity of Zinc-Sodium alginate-Polyethylene glycol- Brucine nanocomposite in gallbladder cancer NOZ cells via modulation of apoptosis and P13K/mTOR pathway

Abstract

Background: Gallbladder cancer (GBC) is the sixth most predominant gastrointestinal tumor worldwide. Malignant tumors with distinctive biological characteristics, like the human GBC, are incredibly aggressive and challenging to diagnose and treat. Objective: The aim of the present study is to explore the in vitro anticancer properties of ZAP-Brucine nanocomposites (ZAP-Bru NCs) on gallbladder cancer cells. Methodology: The cytotoxicity of the ZAP-Bru NCs at concentrations ranging from 10 to 60 µg/mL on the NOZ cells was assessed by an MTT study. The IC50 value of ZAP-Bru NCs was found to be 5 µg/ml, which indicates that it has 50% inhibitory effects on NOZ cells than other doses. Several fluorescent staining approaches, such as dual staining and rhodamine-123 techniques, were applied to investigate the apoptosis and MMP levels in the treated NOZ cells. The generation of ROS in the treated NOZ cells was examined by DCFH-DA staining. The modifications in the expressions of inflammatory genes like NF-κB, TNF-α, IL-6, COX-2, and IL-6 in the treated NOZ cells were examined using the respective kits. Results: ZAP-Bru NCs treatment effectively induced apoptosis in NOZ cells by increasing late and early apoptotic cell numbers. ZAP-Bru NCs also enhanced mitochondrial apoptosis through Bcl-2 protein-dependent signaling. NOZ cells phosphorylated PI3K, Akt, cyclin D1, and mTOR in response to ZAP-Bru NCs treatment. ZAP-Bru NCs treatment also inhibited the phosphorylation of Akt and mTOR in the NOZ cells. Compared to the control group, ZAP-Bru NCs-treated NOZ cells demonstrated significantly fewer proliferative cells and more apoptotic cells. Conclusion: Accordingly, ZAP-Bru NCs could be talented medications against gallbladder cancer.

Keywords

• Cytotoxicity
• NOZ cells
• Apoptosis
• Nanomedicines
• PI3K/Akt/mTOR pathway