The role of Algerian Ephedra alata ethanolic extract in inhibiting the growth of breast cancer cells by inducing apoptosis in a p53- dependent pathway

BACKGROUND: Ephedra alata, a member of the Ephedraceae family, was used to treat different diseases and it might be shown a strong efficacy to inhibit cancer cell lines. METHODS: Due to the limited research available about this plant, the objective of this research was to evaluate the antioxidant, cytotoxic and apoptotic effects of Ephedra alata ethanolic extract (EAEE), against different human cancer cell lines. RESULTS: EAEE inhibited the growth of the liver (HepG2), breast (MCF-7), and colon cancer cells (Caco-2). MCF-7 cells with an IC(50) of 153 µg/ml, were the most sensitive to the extract. Furthermore, exploration using flow cytometry using Annexin V-FITC/PI assay demonstrated that EAEE caused death for all human cancer cells mainly through apoptosis. Very interestingly, qRT-PCR analysis using the ΔΔCt method revealed that four genes, Bax, p21, RB1, and TP53 were up-regulated in MCF-7 cells treated either with EAEE or S-FU drug. These findings let us believe that the mechanism by which EAEE kills breast cancer cells seems to be apoptosis via a P53-dependent manner, which involved intrinsic pathways through the induction of Bax, p21, and RB1. CONCLUSIONS: EAEE exhibits good biological properties in contradiction of HepG-2, MCF-7, and Caco-2 cell lines. This study appoints for the first time that EAEE increases the expression in MCF-7 cells of p53 and three more genetic traits that control cellular proliferation and apoptosis. Therefore, this plant could serve as a potential source to find new pro-apoptotic drugs for cancer treatment.