Chalepin suppresses cell growth by down-regulation of the epidermal growth factor receptor downstream pathways and induced cell cycle arrest in MCF7 breast cancer cells

Abstract:

The Epidermal Growth Factor Receptor (EGFR) pathway is an important signaling cascade currently investigated for its involvement in cancer therapy. In this study, chalepin isolated from Ruta angustifolia was evaluated for its down regulatory activity on the EGFR signaling cascade and possible cell cycle arrest mechanism(s) against MCF7 cancer cell line. Cell cycle analysis was conducted using flow cytometry and protein expression was analyzed using conventional western blotting. The results indicated significant arrest of MCF7 cells at S-phase. Moreover, chalepin induced downregulation of EGFR and its downstream signaling cascades. It also induced upregulation of P21, P27, and tumor suppressor protein P53. Conversely, expression of the cell cycle regulatory proteins cyclin A and D, as well as cyclin-dependents kinases; CDK2 and CDK4, were all downregulated. The present study indicated chalepin possible cell growth inhibitory mechanisms through downregulation of the EGFR signaling pathway, thus promoting cell death in MCF7 cells. Chalepin compound could therefore be consider as a source of anticancer agent to be develop for treatment of cancer such as breast cancer in addition to the existing drugs.

Keywords: Chalepin, EGFR, Cell Cycle, Cellular Signaling, MCF7.

Biography:

Dr. Isah Musa Fakai studied Biochemistry at Usmanu Danfodiyo University, Sokoto and University of Ilorin, Nigeria and graduated with BSc in 2005 and MSc in 2011 respectively. He joined the research group of Prof. Datin Sri Nurestri and Prof. Saiful at the Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia. He received his PhD degree in 2020 at the same institution. He is a Senior Lecturer at the Department of Biochemistry, Faculty of Life Sciences, Abdullahi Fodio University of Science and Technology, Aliero (Formerly Kebbi State University of Science and Technology, Aliero. Nigeria.) Nigeria. He has published more than 50 research articles in a peer reviewed journals and attended as well as presented over 70 papers at both local and international conferences.