Chemopreventive effects of early-stage and late-stage supplementation of vitamin E and selenium on esophageal carcinogenesis in rats maintained on a low vitamin E/selenium diet

Abstract

Low vitamin E and selenium (Ve/Se) nutritional status is known to be associated with increased risk of esophageal squamous cell carcinoma (ESCC). A previous human intervention trial demonstrated that Ve/Se supplementation decreased the occurrence of esophageal cancer death among younger participants but not among older ones. In this study, we intended to mimic this human nutritional status to determine the chemopreventive effects of Ve/Se supplementation at the early or late stage of esophageal carcinogenesis in rats maintained on a low Ve/Se diet. ESCC was induced in F344 rats with N-nitrosomethylbenzylamine (NMBzA) (0.35 mg/kg body wt, subcutaneously, three times per week for 5 weeks). The rats were maintained on a modified AIN-93M diet with low levels of Ve/Se or supplementation to the normal level by using the AIN-93M diet. At Week 25, the numbers of visible tumors and ESCC were significantly lower in rats on AIN-93M diet during the entire experimental period (Group D) or during the early stage (Group B) but not during the late stage (Group C). Ve/Se supplementation (switching from the low Ve/Se diet to the AIN-93M diet) also decreased cell proliferation, angiogenesis, 8-hydroxy-2'-deoxyguanosine, biosynthesis of prostaglandin E2 and leukotriene B4, expression of cyclooxygenase 2 and 5-lipoxygenase in the esophagus. Our results demonstrated that Ve/Se supplementation inhibited NMBzA-induced esophageal carcinogenesis in rats on low Ve/Se diet, and supplementation during the early stage is more effective than during the late stage of carcinogenesis.

Cancer Prevention Research in China

“…This is consistent with the result of a parallel trial on subjects with esophageal dysplasia, showing that supplementation with multiple micronutrients did not produce a significant beneficial effect (15). Studies in a rat model also demonstrated that insufficiencies in vitamin E and selenium enhanced methylbenzylnitrosamine-induced esophageal carcinogenesis, and supplementation with these nutrients at the early stage (but not the late stage) of carcinogenesis had a protective effect (16).…”

Randomized Phase II Trial of Lyophilized Strawberries in Patients with Dysplastic Precancerous Lesions of the Esophagus

“…Many of the known compounds have antioxidant and antiinflammatory activities and protect against cancer including ellagic acid (30), anthocyanins (31, 32), ascorbic acid (vitamin C; ref. 33), calcium (34), and selenium (35). The effective chemical composition of strawberries has not been fully determined.…”

Combination of Selenium and Green Tea Improves the Efficacy of Chemoprevention in a Rat Colorectal Cancer Model by Modulating Genetic and Epigenetic Biomarkers

“…Considerable data from animal and human studies indicate that combinations of dietary agents are more effective than a single agent [17], [18]. For instance, green tea has been shown to synergistically or additively increase the efficacy of other drugs or dietary agents in vitro and in vivo [19]–[22].…”

“…Although preclinical and clinical reports of combining Se and green tea are lacking, combination approaches with Se or green tea have been studied in colon cancer and other cancer models [23]. For instance, a combination of Se and genistein has been shown to inhibit breast cancer in a rat model [24]; a combination of Se and vitamin E has provided greater protection against esophageal carcinogenesis in rats [22]. The combination of green tea and curcumin or the combination of green tea and sulindac has resulted in synergistic chemopreventive effect in an AOM CRC model [25], [26].…”