Abstract
Background: Cancer is a dangerous threat that creates extremely high rates of death and morbidity in various regions of the world. Finding suitable therapeutics to improve cancer therapy while avoiding side effects is critical. The most appropriate innovative therapeutics, which combine natural ingredients and nanomaterials, can improve the biological activity of cancer chemotherapeutics. Methods: Phenolic profiling using high-resolution mass spectrometry and the synthesis of zinc oxide nanoparticles was achieved through the reaction of zinc acetate with Euphorbia retusa extract. The characterization of ZnONPs was performed by UV, IR, Zeta potential, XRD, SEM, and TEM. The cytotoxic activity of the ZnONPs was evaluated using a SRB assay against lung, liver, and breast cancer cell lines. Moreover, the mechanism of cytotoxic activity was evaluated in the form of caspase-8 promoters and anti-inflammatory mechanisms using the Western blot method. Results: The high-resolution LC/MS/MS of the E. retusa led to the identification of 22 compounds in the plant for the first time. The Er-ZnONPs had hexagonal shapes, were approximately 100 nm in size, and consisted of aggregated particles of about 10 nm. The E. retusa ZnONPs exhibited cytotoxic activity against HA-549 (IC50 = 22.3 mu g/mL), HepG2 (IC50 = 25.6), Huh-7 (IC50 = 25.7), MCF-7 (IC50 = 37.7), and MDA-MB-231 (IC50 = 37). Conclusions: E. retusa are rich in phenolics that are capable of synthesizing ZnONPs, which possess cytotoxic activity, via caspase-8 promotion and anti-inflammatory mechanisms.