SCREENING FOR INHIBITORS OF ZEB1, A KEY REGULATOR OF EPITHELIAL TO MESENCHYMAL TRANSITION (EMT) IN BREAST CANCER CELLS.

Abstract

Background: Breast cancer (BC) has an estimated new cases of about 2.3 million individuals and approximately 685,000 deaths in 2020, thereby making it the most common cause of mortality in women. Different subtypes of BC are categorized breast into three clinical subtypes based on the expression or lack of hormone receptors: progesterone (PR), estrogen (ER), and human epidermal growth factor receptor 2 (Her2). Despite the considerable progress made in the treatment of the various types of BC, more research is still needed to address some major obstacles in breast cancer treatment, especially those associated with poor prognosis and reduced survival rates among BC patients like chemoresistance and cancer metastasis; these processes are mediated by Zeb1, which is the key regulator of the EMT. Methods: Cell culture was used to propagate MCF7 cell lines and do transfection. Western blot was used to assess the effects on the markers of EMT such as Zeb1 and Cdh1. Cell cycle analysis using flow cytometry was used to examine candidate inhibitors of EMT after induction of Zeb1. Results: The induced MCF7 cells show a higher percentage of cell cycle arrests at the G1 phase than non-induced cells after treatment with candidate inhibitors. Conclusion: Out of the three PKC inhibitors tested midostaurin, auranofin, and resveratrol; resveratrol demonstrated a more significant impact on Zeb1-expressing cells than those without expression of Zeb1 by decreasing the percentage of cells at the G1 phase, hence, resveratrol might directly interfere with the activity of Zeb1