Simultaneous Treatment With Benzyl Isothiocyanate, a Strong Bladder Promoter, Inhibits Rat Urinary Bladder Carcinogenesis by N-Butyl-N-(4-Hydroxybutyl)Nitrosamine

Okazaki, Kazushi; Yamagishi, Megumi; Son, Hwa–Young; Imazawa, Takayoshi; Furukawa, Fumio; Nakamura, Hideaki; Nishikawa, Akiyoshi; Masegi, Toshiaki; Hirose, Masao

doi:10.1207/s15327914nc422_10

Cited by 33 publications

(26 citation statements)

References 24 publications

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“…However, some other ITC have been reported to be carcinogenic in rats. [27][28][29][30][31][32] Especially, allyl isothiocyanate was reported to be carcinogenic for male F344 rats in the urinary bladder, but was not carcinogenic for B6C3F1 mice of either gender. 27 High cruciferous vegetable consumption is suggested to reduce bladder cancer risk from epidemiological study.…”

Section: Discussionmentioning

confidence: 99%

“…In their study, PEITC treatment did not affect the BBN-induced bladder tumorigenesis and PHITC suppressed bladder tumor development. Okazaki et al 32 found that simultaneous treatment of BITC and BBN inhibits BBN-induced urinary bladder carcinogenesis in F344 rat. Those findings suggest that modifying effects of ITC on the urinary bladder carcinogenesis are depended to the difference of rodent species and strains, chemicals and treatment schedule.…”

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confidence: 99%

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Suppressive effect of 1,4-phenylene diisothiocyanate onN-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary bladder carcinogenesis in male ICR mice

Sugie¹,

Vinh²,

Rahman³

et al. 2005

Int. J. Cancer

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The modifying effects of dietary administration of 1,4-phenylene diisothiocyanate (DITC) on N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced urinary bladder carcinogenesis during the initiation and post-initiation phases were examined in male ICR mice. Five-week-old animals were divided into 5 groups. Groups 1-3 were given BBN (500 ppm) in drinking water for 6 weeks starting at age 6 week. Mice in Group 2 were given the diet containing 100 ppm DITC for 8 weeks during the initiation phase, starting 1 week before BBN exposure. Animals in Group 3 were fed the experimental diet for 24 weeks during the post-initiation phase starting 1 week after the cessation of BBN exposure. Mice in Group 4 were given only the diet containing the test compound, and those in Group 5 were given the basal diet alone throughout the experiment (32 weeks). The frequency of bladder lesions, neoplasms, dysplasia and hyperplasia, was analyzed histopathologically. The cell-proliferation activity estimated by the 5-bromodeoxyuridine labeling index (BrdU-LI), and cell cycle progression by counting cyclin D1-positive cell ratios were compared among the groups using immunohistochemistry. Administration of DITC in the initiation phase reduced significantly the incidence of urinary bladder carcinoma and dysplasia. The frequencies of any lesions of urinary bladder were not reduced by DITC in post-initiation phase. Dietary exposure of this agent in initiation phase reduced significantly both BrdU-LI and cyclin D1-positive cell ratios in any bladder lesions. Administration of DITC in post-initiation phase also significantly reduced BrdU-LI in bladder neoplasms and hyperplasia and cyclin D1-positive cell ratios in urinary bladder carcinoma as well as dysplasia. These results suggest that dietary DITC could be a preventive agent against BBNinduced bladder carcinogenesis in mice when fed during the initiation phase. ' 2005 Wiley-Liss, Inc.Key words: chemoprevention; DITC; BBN; cyclin D1; BrdU labeling index; urinary bladder carcinogenesis Epidemiologic studies suggest that the consumption of green and yellow vegetables has an inverse relationship with cancer risk. [1][2][3][4][5][6][7] Organosulfur compounds that are present abundantly in a group of cruciferous vegetables or allium species have been shown to possess cancer chemopreventive properties. [8][9][10] Especially, isothiocyanates (ITC) are versatile chemopreventive agents in many animal systems.Cancer prevention studies of our group have demonstrated that benzyl isothiocyanate (BITC) inhibit methylazoxymethanol (MAM)-acetate induced intestinal carcinogenesis and diethylnitrosamine (DEN) induced hepatocarcinogenesis in rats, and sinigrin reduced 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis and DEN-induced hepatocarcinogenesis.11-14 We also found that BITC reduced not only unscheduled DNA synthesis (UDS) but also replicative DNA synthesis (RDS), induced by some genotoxic carcinogens, e.g., 2-acetylaminofluorene (AAF), MAM acetate, 9,10-dimethyl-1,2-benzanthracene (DMBA), and DEN....

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Suppressive effect of 1,4-phenylene diisothiocyanate onN-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary bladder carcinogenesis in male ICR mice

Sugie¹,

Vinh²,

Rahman³

et al. 2005

Int. J. Cancer

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“…Using a cell culture system, we previously showed that dietary isothiocyanates and their urinary metabolites (NAC-ITCs) exerted potent antiproliferative effects on human bladder cancer cells at in vivo -achievable concentrations (4-7). The induction of carcinogendetoxifying phase 2 enzymes and the inhibition of carcinogen-induced carcinogenesis in the bladder of animals has also been reported (8,9). It is highly possible that intake of isothiocyanate-rich cruciferous vegetables has a preventive effect on human bladder cancer, and such protective effects may, to a certain extent, correspond to the amount of isothiocyanates provided by these vegetables.…”

Section: Cancer Epidemiology Biomarkers and Prevention Cancer Epidemiomentioning

confidence: 93%

“…Bladder cancer is particularly interesting because dietary isothiocyanates, a group of key anticarcinogens occurring in cruciferous vegetables, show potent chemopreventive effects against bladder cancer in both in vitro and in vivo models (4)(5)(6)(7)(8)(9). Moreover, the unique in vivo pharmacokinetics and disposition of orally ingested isothiocyanates in humans renders the bladder the best targeted organ for the anticancer effect of dietary isothiocyanates (5).…”

Section: Introductionmentioning

confidence: 99%

Consumption of Raw Cruciferous Vegetables is Inversely Associated with Bladder Cancer Risk

Tang¹,

Zirpoli²,

Guru

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

138

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Cruciferous vegetables contain isothiocyanates, which show potent chemopreventive activity against bladder cancer in both in vitro and in vivo studies. However, previous epidemiologic studies investigating cruciferous vegetable intake and bladder cancer risk have been inconsistent. Cooking can substantially reduce or destroy isothiocyanates, and could account for study inconsistencies. In this hospital-based case-control study involving 275 individuals with incident, primary bladder cancer and 825 individuals without cancer, we examined the usual prediagnostic intake of raw and cooked cruciferous vegetables in relation to bladder cancer risk. Odds ratios (OR) and 95% confidence intervals (CI) were estimated with unconditional logistic regression, adjusting for smoking and other bladder cancer risk factors. We observed a strong and statistically significant inverse association between bladder cancer risk and raw cruciferous vegetable intake (adjusted OR for highest versus lowest category = 0.64; 95% CI, 0.42-0.97), with a significant trend (P = 0.003); there were no significant associations for fruit, total vegetables, or total cruciferous vegetables. The associations observed for total raw crucifers were also observed for individual raw crucifers. The inverse association remained significant among current and heavy smokers with three or more servings per month of raw cruciferous vegetables (adjusted ORs, 0.46 and 0.60; 95% CI, respectively). These data suggest that cruciferous vegetables, when consumed raw, may reduce the risk of bladder cancer, an effect consistent with the role of dietary isothiocyanates as chemopreventive agents against bladder cancer. (Cancer Epidemiol Biomarkers Prev 2008; 17(4):938 -44)

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“…These bioactive compounds act via multiple mechanisms, such as cancer cell signalling, proliferation, apoptosis, migration and invasion, as well as angiogenesis and carcinogen elimination , Zhang, 2004, Thornalley, 2002, Nakamura and Miyoshi, 2006, Wu et al, 2009, Navarro et al, 2011, Wahle et al, 2011, Soobrattee et al, 2006, Tanaka et al, 2012, Van Breemen and Pajkovic, 2008, to exhibit in vitro and in vivo anticancer activities. BG: 12.7 µmol/g seed, < 0.03 µmol/g pulp BITC: 4.6 µmol/g seed, < 0.003 µmol/g pulp (Nakamura et al, 2007) In vivo animal studies in rat, mouse or hamster for inhibitory effect on:  intestinal carcinogenesis (Sugie et al, 1994)  hepatocarcinogenesis (Sugie et al, 1993)  lung tumourigenesis and metastasis (Kim et al, 2011a, Hecht et al, 2000, Hecht et al, 2002  pancreatic carcinogenesis (Kuroiwa et al, 2006)  urinary bladder carcinogenesis (Okazaki et al, 2002)  mammary carcinogenesis (Warin et al, 2009).…”

Section: Phytochemicals In Carica Papaya With Reported Anticancer Actmentioning

confidence: 99%

Investigation of bioactive compounds with anti-cancer potential in Carica papaya leaves

Nguyen¹

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Carica papaya is widely cultivated in tropical and subtropical countries and is used as a traditional medicine to treat a range of diseases as well as a foodstuff. Increasing anecdotal reports of the use of papaya leaf in successful cancer treatment and prevention have warranted the scientific authentication of the pharmacological properties of papaya leaf. An extensive review that was conducted at the beginning of this study further confirmed that more research is needed to explore the bioactive compounds in C. papaya for their anticancer activities. contents were measured and found to be elevated in these two acidic serial extracts.

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Simultaneous Treatment With Benzyl Isothiocyanate, a Strong Bladder Promoter, Inhibits Rat Urinary Bladder Carcinogenesis by N-Butyl-N-(4-Hydroxybutyl)Nitrosamine

Cited by 33 publications

References 24 publications

Suppressive effect of 1,4-phenylene diisothiocyanate onN-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary bladder carcinogenesis in male ICR mice

Suppressive effect of 1,4-phenylene diisothiocyanate onN-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary bladder carcinogenesis in male ICR mice

Consumption of Raw Cruciferous Vegetables is Inversely Associated with Bladder Cancer Risk

Investigation of bioactive compounds with anti-cancer potential in Carica papaya leaves

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