Mechanistic Insights into ROS-Mediated Apoptosis Induced by Green-Synthesized Embelia ribes-Derived Zinc Oxide Nanoparticles in Human Triple-Negative Breast Cancer Cells

Abstract

Despite advances in surgical treatment, chemotherapy, hormone therapy, and targeted therapies, breast cancer continues to be one of the top cancers responsible for deaths due to cancers among women, with around 2.3 million cases diagnosed per year. The development of drug resistance, metastasis, recurrence, and associated toxicity continues to be issues that hinder successful treatment of the disease. Nanotechnology provides a viable solution for cancer treatment owing to its physicochemical properties.The present research involved the preparation of zinc oxide nanoparticles (ZnO NPs) through seed extract of Embelia ribes, which were used for their anti-cancer property against breast cancer cells, MDA-MB-231. Biosynthesis of ZnO NPs was done through characterization methods, such as UV-Visible spectrometry, FTIR Spectrometry, and X-Ray Diffraction analysis. UV-visible spectrometry was used for the validation of biosynthesis of nanoparticles as there was an absorption peak found in the wavelength region between 330–340 nm, while FTIR Spectrometry identified the presence of functional groups, such as hydroxyl, carbonyl, and amine groups, which were phytochemical groups responsible for the reduction and stabilization of the nanoparticles. Biological evaluation involved the observation of the cytotoxic effects in a dose-dependent manner against MDA-MB-231 cells with the highest cytotoxicity effect being similar to that of doxorubicin at 200 µg/mL.Enhanced ROS levels due to the presence of oxidative stress were measured through DCFH-DA analysis. Moreover, the AO/EtBr assay showed the apoptotic features of the ZnO NPs. The results indicate that ZnO NPs synthesized using Embelia ribes have great potential as anticancer agents via ROS-induced apoptosis and can act as green nanotherapy for treating breast cancer. Further research is needed for their validation as therapeutic agents.