Chemoprevention of mouse urinary bladder carcinogenesis by fermented brown rice and rice bran

Abstract

Abstract. Fermented brown rice by Aspergillus oryzae (FBRA) has been shown to be a potent anti-carcinogenic compound. Here, we investigated the modifying effects of dietary feeding with a naturally occurring anti-oxidant FBRA on N-butyl-N-(4-hydroxybutyl)-nitrosamine (OH-BBN)-induced urinary bladder carcinogenesis in male ICR mice. Five-week-old male ICR mice were divided into 7 groups, and groups 1-5 were given OH-BBN (500 ppm) in drinking water for 6 weeks starting at 7 weeks of age. Groups 2 and 3 were fed the diet containing 5% and 10% FBRA during the initiation phase, respectively, whereas groups 4 and 5 were fed these diets during the post-initiation phase. Group 6 was given the diet containing 10% FBRA throughout the experiment, and group 7 was kept on the basal diet alone and served as an untreated control. At the end of the study (week 32), the incidences of simple hyperplasia, dysplasia and carcinoma in the bladders of group 1 (OH-BBN alone) were 92%, 49% and 38%, respectively. Those of group 5 (64%, 23% and 10%) and the incidence of carcinoma of group 4 (17%) was significantly less than that of group 1. Furthermore, the multiplicity of simple hyperplasia and carcinoma of group 5 was significantly less than that of group 1. Postinitiation exposure of 10% FBRA significantly decreased the number/nucleus of silver-stained nucleolar organizer region proteins (AgNORs), an index of cell proliferation, in the non-lesional transitional epithelium when compared to that of the control. Our results indicate that FBRA exerts chemopreventive effects against chemically induced urinary bladder carcinogenesis through anti-proliferative mechanisms. FBRA could be a promising chemopreventive agent for human urinary bladder cancer. IntroductionBladder cancer is the 7th most common cancer worldwide, with an estimated 336,000 new cases occurring each year (1). In Japan, the incidence and mortality rates of this malignancy are lower compared with Western populations, but have gradually increased (2,3). The occurrence of neoplasms in the urinary tract epithelium is known to relate to multistage and multifocal carcinogenesis. A high recurrence rate of superficial bladder tumors, even after curative transurethral resection, has often been reported (4). These successive, recurrent tumors may increase in their histological grade, and more than 15% of the patients are predicted to suffer the progression with subsequent poor prognosis (5,6). A number of anticancer drugs have been used, mainly via local instillation into the bladder, as an adjuvant to surgery to suppress or prevent tumor recurrence. However, only a few drugs have been regarded as effective agents. Therefore, a new modality is required to achieve a more satisfactory clinical control of this malignancy.One approach to curb cancer incidence is chemopreventive intervention through which the disease can be totally prevented, delayed, or fixed dormant by the administration of one or more naturally occurring and synthetic chemical agents. Certain synthetic compounds, such...

Chemopreventive effect of fermented brown rice and rice bran (FBRA) on the inflammation-related colorectal carcinogenesis in ApcMin/+ mice

“…A number of studies have shown the chemopreventive effect of fermented brown rice and rice bran (FBRA) on several types of cancer, including colon cancer (12)(13)(14)(15). In contrast to previous findings that FBRA significantly suppressed azoxymethane-induced colorectal carcinogenesis in rats, in the present study, FBRA has no effect on the tumor development of the colon in Apc Min/+ genetic background.…”

“…Fermented brown rice and rice bran (FBRA) is a processed food prepared by fermented the brown rice and rice bran with Aspergillus oryzae. In our previous studies, FBRA showed chemopreventive effect against various types of chemically-induced cancer, including colon (12), stomach (13), bladder (14) and esophagus (15) …”

Evaluation of the cancer chemopreventive efficacy of rice bran in genetic mouse models of breast, prostate and intestinal carcinogenesis

“…A brown rice preparation (2.5 or 5% in the diet), obtained by fermentation with Aspergillus oryzae, interfered with azoxymethane-induced formation of aberrant crypt foci and adenocarcinomas in rats (Katayama et al, 2002). Furthermore, fermented brown rice reduced diethylnitrosamine-and phenobarbital-induced hepatocarcinogenesis in rats (Katayama et al, 2003), N-nitrosomethylbenzylamine-induced oesophageal tumorigenesis in rats (Kuno et al, 2004) and bladder carcinogenesis in mice (Kuno et al, 2006). To our knowledge there is no information in the literature on the epidemiology, linking consumption of brown rice or rice bran to colorectal cancer risk in humans, which would complement the available data in animal models.…”

Chemopreventive Properties of Dietary Rice Bran: Current Status and Future Prospects

“…In addition to colonic and gastric cancers, fermented brown rice has demonstrated chemopreventive effects against cancers of the lung, liver, bladder, tongue, and esophagus (28)(29)(30)(31)(32). All of these studies were able to demonstrate that the feeding of fermented brown rice to carcinogen-treated mice significantly decreased the incidence and multiplicity of the tumors in the respective tissues.…”