title: Quercetin reverses EGF-induced epithelial to mesenchymal transition and invasiveness in prostate cancer (PC-3) cell line via EGFR/PI3K/Akt pathway.
abstract: Epidermal growth factor (EGF) plays an important role in metastasis and tumorigenesis of prostate cancer. Epithelial-mesenchymal transition (EMT) is a process in tumor progression during which cancer cells undergo dramatic changes acquiring highly invasive properties. The purpose of this study was to determine the effect of quercetin on EGF-induced EMT in prostate cancer (PC-3) cell line. Quercetin, a plant flavonoid, prevented EGF-induced invasion and migration of PC-3 cells. The protein and mRNA expressions of E-cadherin and N-cadherin were studied by immunocytochemistry, Western blotting and real-time polymerase chain reaction. Quercetin prevented EGF-induced expression of N-cadherin and vimentin and increased the expression of E-cadherin in PC-3 cells, therefore preventing EGF-induced EMT. EGF-induced cell adhesion proteins, intercellular adhesion molecule and vascular cell adhesion molecule were significantly decreased by quercetin treatment. Furthermore, mRNA and protein expressions of Snail, Slug and Twist showed that quercetin significantly decreased EGF-induced expressions of Snail, Slug and Twist. The protein expressions of epidermal growth factor receptor (EGFR)/phosphatidylinositide 3-kinases (PI3K)/Akt/extracellular signal-regulated kinase (ERK)1/2 pathway showed that quercetin prevents EGF-induced EMT via EGFR/PI3k/Akt/ERK1/2 pathway and by suppressing transcriptional repressors Snail, Slug and Twist in PC-3 cells. Thus, it is concluded from the present study that quercetin may prevent cancer metastasis by targeting EMT.
authors.affiliation: Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, 600113, India.
authors.forename: Firdous Ahmad
authors.initials: FA
authors.lastname: Bhat
authors.affiliation: Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, 600113, India.
authors.forename: G
authors.initials: G
authors.lastname: Sharmila
authors.affiliation: Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, 600113, India.
authors.forename: S
authors.initials: S
authors.lastname: Balakrishnan
authors.affiliation: Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, 600113, India.
authors.forename: R
authors.initials: R
authors.lastname: Arunkumar
authors.affiliation: Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, 600113, India.
authors.forename: P
authors.initials: P
authors.lastname: Elumalai
authors.affiliation: Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, 600113, India.
authors.forename: S
authors.initials: S
authors.lastname: Suganya
authors.affiliation: Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, 600113, India.
authors.forename: P
authors.initials: P
authors.lastname: Raja Singh
authors.affiliation: Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, 600113, India.
authors.forename: N
authors.initials: N
authors.lastname: Srinivasan
authors.affiliation: Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, 600113, India. Electronic address: j_arunakaran@hotmail.com.
authors.forename: J
authors.initials: J
authors.lastname: Arunakaran
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors* / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D011493:Protein Kinase C / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D017931:DNA Primers; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D004815:Epidermal Growth Factor; D011794:Quercetin; D019869:Phosphatidylinositol 3-Kinases; C089212:protein kinase D; D066246:ErbB Receptors; D011493:Protein Kinase C
keywords: E-cadherin; Epidermal growth factor; Epithelial–mesenchymal transition; N-cadherin; Vimentin