Abstract.Resveratrol is a small polyphenol that has been intensively studied in a wide spectrum of therapeutic fields. More recently, resveratrol has been demonstrated to exert its antitumor activity in numerous tumor models. The present study reported that resveratrol exhibited a marked anti-proliferative effect on human esophageal squamous cell carcinoma (ESCC) cells by inducing cell cycle G 0 /G 1 phase arrest and cell death, which was associated with a decrease in the expression levels of cyclin D1 and an increase in cleaved PARP/cleaved caspase-3 expression levels. The mechanisms underlying the antitumor potency of resveratrol were principally attributed to the downregulation of epidermal growth factor receptor (EGFR) signaling. The western blotting results showed that exposure of ESCC cells to resveratrol inhibited EGF-induced EGFR activation in addition to decreasing the total protein levels of EGFR and membrane/nuclear localization. In summary, the results suggested that resveratrol, or an associated analog, may have a role in the management of human ESCC.
IntroductionHuman esophageal squamous cell carcinoma (ESCC) is the 6th leading cause of cancer-associated mortality, and the 8th most common type of cancer worldwide (1). ESCC is the most common histology of esophageal cancers, and has a high incidence in China, South Africa, France and Italy (2). Epidemiological and etiological studies have previously demonstrated that certain environmental and genetic factors have crucial roles in esophageal carcinogenesis (3-7). Although there have been advances in the fields of surgery and chemotherapy, the prognosis for ESCC is typically poor as the majority of patients diagnosed are elderly and present with advanced-stage disease, rendering them unsuitable for curative resection and maintaining the five-year survival rate for ESCC at <15% (1). Therefore, improving the current understanding of the molecular mechanisms underlying ESCC pathogenesis and identifying effective therapeutic agents are required to facilitate the development of novel therapies for this disease.Resveratrol is present in red grapes, wine, nuts and common garden plants, and is one of the most intensively investigated of all the phytochemicals with putative beneficial effects on human health (8). The effects of resveratrol include anti-oxidant and anti-aging properties, improvement of insulin sensitivity and reduction of cardiovascular disease risk (9-11). Previous studies have also indicated that resveratrol is able to function as a chemo preventive and chemotherapeutic agent in certain types of human carcinomas, including those of the colorectum, skin, liver, lung, pancreas, breast and prostate (8,(12)(13)(14). Previous studies suggesting that a dietary pattern rich in resveratrol may reduce the risk of ESCC (15). However, the molecular mechanisms underlying resveratrol-induced antitumor effects have yet to be elucidated. A number of potential mechanisms have been suggested to be involved in resveratrol-induced cancer preventative effects, i...