title: Quercetin, a natural dietary flavonoid, acts as a chemopreventive agent against prostate cancer in an in vivo model by inhibiting the EGFR signaling pathway.
abstract: Prostate cancer incidence and mortality rates have increased over the past years. The purpose of the present study was to examine the molecular mechanism underlying the chemopreventive effects of quercetin on prostate cancer in an in vivo model. Sprague-Dawley male rats were divided into four groups, Group I: vehicle control (propylene glycol), Group II: chemically induced cancer model (MNU + T); Group III: chemically induced cancer model + quercetin (200 mg per kg b.w.); Group IV: quercetin (200 mg per kg b.w.). Serum levels of quercetin were assessed by high performance liquid chromatography (HPLC). EGFR, PI3K/Akt protein levels were significantly increased in chemically induced cancer rats, which were brought back to normalcy in both DLP & VP (dorsolateral prostate & ventral prostate) by quercetin supplementation. Also, the protein expression levels of proliferating cell nuclear antigen (PCNA), N-cadherin, vimentin, and cyclin D1 exhibited a significant increase in both DLP & VP of chemically induced cancer rats. However, simultaneous quercetin supplementation significantly decreased PCNA, N-cadherin, vimentin, and cyclin D1 protein levels compared to chemically induced cancer rats. The E-cadherin expression was decreased in chemically induced cancer animals. Simultaneous quercetin supplementation prevented it. Real time PCR was used to study the mRNA expression of snail, slug and twist. Quercetin significantly decreased snail, slug, and twist mRNA levels in chemically induced cancer rats. To conclude from the present study, quercetin was effective in preventing prostate cancer progression by inhibiting the EGFR signaling pathway and by regulating cell adhesion molecules in Sprague Dawley rats.
authors.affiliation: Department of Endocrinology, Dr ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai-600113, India. J_arunakaran@hotmail.com.
authors.forename: A B
authors.initials: AB
authors.lastname: Firdous
authors.forename: G
authors.initials: G
authors.lastname: Sharmila
authors.forename: S
authors.initials: S
authors.lastname: Balakrishnan
authors.forename: P
authors.initials: P
authors.lastname: RajaSingh
authors.forename: S
authors.initials: S
authors.lastname: Suganya
authors.forename: N
authors.initials: N
authors.lastname: Srinivasan
authors.forename: J
authors.initials: J
authors.lastname: Arunakaran
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D018890:Chemoprevention / Q000379:methods; D002851:Chromatography, High Pressure Liquid; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D059808:Polyphenols / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D011794:Quercetin / Q000097:blood / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D015820:Cadherins; D059808:Polyphenols; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D014746:Vimentin; D019938:Cyclin D1; D011794:Quercetin; D019869:Phosphatidylinositol 3-Kinases; C483803:Egfr protein, rat; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt