Chemoprevention of metaplasia initiation and carcinogenic... : Anti-Cancer Drugs (original) (raw)
PRECLINICAL REPORTS
Chemoprevention of metaplasia initiation and carcinogenic progression to esophageal adenocarcinoma by resveratrol supplementation
Woodall, Charles E.a; Li, Yana; Liu, Qia Honga; Wo, Johnb; Martin, Robert C.G.a
aDivision of Surgical Oncology, Department of Surgery, James Graham Brown Cancer Center
bDivision of Gastroenterology, University of Louisville School of Medicine, Louisville, Kentucky, USA
Correspondence to Dr Robert C.G. Martin, MD, PhD, Division of Surgical Oncology, Department of Surgery, University of Louisville, Norton Healthcare Pavilion, 315 East Broadway, Suite 313, Louisville, KY 40202, USA
Tel: +502 629 3355; fax: +502 629 3393; e-mail: [email protected]
Received 10 May 2008 Revised form accepted 27 February 2009
Abstract
Resveratrol (3,5,4′-trihydroxy-_trans_-stilbene), a polyphenol found in the skin of the grape and red wine, has been found to have chemopreventitive effects in some carcinogenic models. The effects of resveratrol on the initiation of Barrett's metaplasia and the carcinogenic progression to esophageal adenocarcinoma have not been evaluated. The aim of this study was to evaluate the effects of resveratrol on the transition from reflux esophagitis to Barrett's metaplasia to dysplasia to esophageal adenocarcinoma in an established rat model. Male Sprague–Dawley rats underwent esophagoduodenal anastomosis as per institutional approved protocol. They were then treated twice weekly with intraperitoneal injection of 7 mg/kg of resveratrol or saline. Additional nonoperated rats served as controls. The rats in each group were assigned to 1, 3, or 5-month subgroups. The distal esophagus was preserved for blinded histopathological examination at the time of harvest. Thirty-one animals in the 5-month resveratrol group showed a decreased severity of esophagitis (P<0.0001), incidence of intestinal metaplasia (P = 0.3567), and incidence of carcinoma (P = 0.4590) as compared with both the saline and nonoperated control groups. In conclusion, morphological characteristics consistent with decreased esophagitis and incidences of metaplasia and esophageal adenocarcinoma were seen on histopathology in the resveratrol group. Resveratrol resulted in a small diminution of the carcinogenic effects and progression to metaplasia, and further human studies are designed to explore the potential anticarcinogenic mechanism.
© 2009 Lippincott Williams & Wilkins, Inc.