Protection Against Esophageal Cancer in Rodents With Lyophilized Berries: Potential Mechanisms

Abstract

For several years, our laboratory has been evaluating the ability of lyophilized (freeze-dried) black raspberries (Rubus occidentalis, BRBs), blackberries (R. fructicosus, BBs), and strawberries (Fragaria ananasia, STRWs) to inhibit carcinogen-induced cancer in the rodent esophagus. To assure "standardized" berry preparations for study, each berry type is of the same cultivar, picked at about the same degree of ripeness, washed and frozen within 2-4 h of the time of picking, and freeze-dried under conditions that preserve the components in the berries. Some of the known chemopreventive agents in berries include vitamins A, C, and E and folic acid; calcium and selenium; β-carotene, α-carotene, and lutein; polyphenols such as ellagic acid, ferulic acid, pcoumaric acid, quercetin, and several anthocyanins; and phytosterols such as β-sitosterol, stigmasterol, and kaempferol. In initial bioassays, freeze-dried STRW, BRB, and BB powders were mixed into AIN-76A synthetic diet at concentrations of 5% and 10% and fed to Fischer 344 rats before, during, and after treatment with the esophageal carcinogen Nnitrosomethylbenzylamine (NMBA). At 25 wk of the bioassay, all three berry types were found to inhibit the number of esophageal tumors (papillomas) in NMBA-treated animals by 24-56% relative to NMBA controls. This inhibition correlated with reductions in the formation of the NMBA-induced O 6 -methylguanine adduct in esophageal DNA, suggesting that the berries influenced the metabolism of NMBA leading to reduced DNA damage. Studies are ongoing to determine the mechanisms by which berries influence NMBA metabolism and DNA adduct formation. BRBs and STRWs were also tested in a postinitiation scheme and were found to inhibit NMBA-induced esophageal tumorigenesis by 31-64% when administered in the diet following treatment of the animals with NMBA. Berries, therefore, inhibit tumor promotion and progression events as well as tumor initiation. In vivo mechanistic studies with BRBs indicate that they reduce the growth rate of premalignant esophageal cells, in part, through down-regulation of cyclooxygenase-2 leading to reduced prostaglandin production and of inducible nitric oxide synthase leading to reduced nitrate/nitrite levels in the esophagus. Based upon the preclinical data on rodents, we have initiated prevention trials in humans to determine if berries might exhibit chemopreventive effects in the esophagus.

Cancer prevention with freeze-dried berries and berry components

“…Mechanistic studies indicate that berries affect both the initiation and progression stages of tumor development [56]. Berry components influence carcinogen metabolism with lowered levels of DNA adducts.…”

Antibacterial and Antitumor Activities of Some Wild Fruits Grown in Turkey

“…Some studies about anticancer activities of some Rubus spp. have been recorded (4,10,14,27,41,54,55,57). Saenz et al (51) reported that hexanoic extract of C. monogyna demonstrated significant cytotoxic activity against larynx cancer cells.…”

“…there are many studies about the anticancer activities of Rubus spp. (4,10,14,27,41,54,55,57). Fruits and flowers of many Crataegus spp.…”

Anticancer Activity and Nutritional Value of Extracts of the Seed of Glinus lotoides

“…Recently Suzuki et al showed that consumption of Catalpa ovata seed oil, which is rich in conjugated linolenic acid, suppresses the development of colonic aberrant crypt foci induced by azoxymethane in rats (35). Phytosterols were reported to show significant cancer prevention activity (38). Table 5 shows the macro-nutritional values of the seeds of G. lotoides.…”