The Cytotoxicity Of “Al-Siddir” Tree “Ziziphus Spina Christi” Methanolic Leaves Extract on Her-2 Positive Breast Cancer

Abstract

HER-2 positive is a subtype of breast cancer that acquires poor prognosis and low survival rates. Targeted therapy is one of the main approaches that are used for the treatment of HER-2-positive breast cancer. However, it is associated with several adverse effects and a high chance of drug resistance, which necessitates continuous research to discover novel agents. Medicinal plants are a rich source of many biologically active ingredients that could be potential candidates for anticancer leads. Ziziphus spina-Christi (ZSC) is a plant species that exerts various biological activities, including cytotoxicity, as it contains different essential bioactive constituents. This study is the first to investigate the cytotoxic potential of the methanolic leaves extract of ZSC that is growing in Qatar against HER-2 positive breast cancer cell lines SK-BR-3 and ZR-75-1 on the cellular and molecular levels using different in vitro assays as well as in ovo assay for angiogenesis evaluation using the chicken embryo model. The established ZSC methanolic leaves extract was standardized by RP-HPLC analysis using the flavonoids rutin and quercetin as marker compounds. Biological evaluation revealed that ZSC extract had significantly reduced the viability, altered the morphological features of the cells, induced apoptosis, and inhibited the migration, colony formation, and angiogenesis in both cell lines. Moreover, molecular investigations had revealed that ZSC extract produced its effect by inactivating the HER-2 / p38 MAPK signaling pathway that is mainly involved in the carcinogenesis process and by deregulating different proteins such as Bax, E-cadherin, and NF-κB. These results collectively support the promising cytotoxic potential of ZSC against HER-2-positive breast cancer and allow a basis for further related investigations.