Ibrahim H Kankia
Abertay University, UK
Title: Luteolin upregulate HER1 expression via NRF2-mediated activation leading to increase in normal breast cell proliferation
Biography
Biography: Ibrahim H Kankia
Abstract
Luteolin enhances the increased in normal breast cell growth through NRF2 activation, although the exact mechanism of this activation is still unclear. The HER1 is one of the members of EGFR family which regulate the normal cellular proliferation, differentiation and maintenance. These receptors dimerize upon ligand binding, leading to activation of their tyrosine kinase domain. This subsequently led to the phosphorylation of their tyrosine residues in the intracellular domain. Nuclear factor (NRF2) is a transcription factor that regulates the expression of a battery of many genes including cytoprotective and detoxifying genes. Abnormal expression of both HER1 and NRF2 are reported in tumour initiation and studies have implicated both NRF2 and HER family in numerous cancers. In this study, we demonstrated that luteolin activated the NRF2 activity, which led to maintenance of HER1 protein expression and increased in cell growth of MCF10 cells. Additional investigation revealed that luteolin could lead to transcriptional activation of HER1 promoter activity by activating the NRF2 activity in the HER1 promoter region. Furthermore, activation of NRF2 by luteolin led to increase in total glutathione and other enzymes such as HO-1 and pAKT in the cell line used. Taken together, these data suggest that luteolin may activate the cell proliferation of normal breast cells through NRF2-mediated activation of HER1 expression and could be a novel avenue that luteolin induced NRF2 activation, which lead to increase normal breast cell growth.