Cell based and In vivo systematic evaluation of some Egyptian plant extracts targeting breast cancer

Abstract

The prevalence of breast cancer as a significant public health concern necessitates continued exploration of natural resources for novel anti-cancer agents is crucial. Material and methodsAnticancer activity of plant extracts on monolayer breast cancer cell line (MCF7) with lower levels of toxicity towards normal (RPE1) underwent further assessment using a three-dimensional model (3D). The extract's effects were investigated through multiple assays including apoptosis induction using quantifying cleaved cytokeratin-18 (CK18) and DNA fragmentation. Additionally, the expression of Bcl-2 and Bax was quantitative using real-time PCR. The median lethal dose (LD50) was determined by the acute oral toxicity, while biomarkers associated with tumorigenesis, metastasis, and cell death were quantified by ELISA. ResultsLimoniastrum monopetalum and Bauhinia variegata exhibited the most potent antitumor efficacy among the investigated extracts. They demonstrated potent cytotoxicity against MCF7 with no significant effect on hTERT RPE-1, with an IC50 of 100 μM. The extract demonstrated effectiveness in killing cancer cells within 3D tumor-like structures, induced apoptosis through caspase-3 activation and cleavage of cytokeratin-18, up-regulated the tumor suppressor p53, down-regulated the anti-apoptotic Bcl-2 gene, and caused DNA fragmentation. Acute oral toxicity studies in mice indicated low toxicity, and in a syngeneic mouse tumor model, the extract significantly inhibited tumor growth, suggesting its potential for further development. ConclusionLimoniastrum monopetalum and Bauhinia variegata exhibited the most potent antitumor efficacy among the investigated extracts.