Toxic effects of 4‐methylthio‐3‐butenyl isothiocyanate (<i>Raphasatin</i>) in the rat urinary bladder without genotoxicity

Suzuki, Isamu; Cho, Young‐Man; Hirata, Tadashi; Toyoda, Takeshi; Akagi, Jun‐ichi; Nakamura, Yasushi; Sasaki, Akira; Nakamura, Takako; Okamoto, Shigehisa; Shirota, Koji; Suetome, Noboru; Nishikawa, Akiyoshi; Ogawa, Kumiko

doi:10.1002/jat.3384

Cited by 11 publications

(7 citation statements)

References 29 publications

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“…Regarding cell cycle arrest, previous studies have found that sulforaphene inhibits proliferative activity by increasing the expression of p21 (cyclin-dependent kinase inhibitor), which in turn promotes G1 cell cycle phase arrest (esophageal carcinogenesis in vivo). By contrast, sulforaphene induces apoptosis through increased expression of p21 (32), downregulation of the B-cell lymphoma-2 (Bcl-2)/apoptosis regulator BAX (Bax) ratio (in vivo) and activation of caspase-3 and -9 (in vitro, A549 lung cancer cells) (46). In the present study, few apoptotic cells were observed following 3-BI treatment of PC-3 cells, suggesting that the effect of 3-BI could be mediated through other pathways, which will be investigated in future studies.…”

Section: Discussionmentioning

confidence: 98%

“…1). ITCs have inhibitory effects on the metabolic activation of carcinogenic dietary or tobacco components (24), along with the inhibition of mutagenesis (25) and anti-carcinogenic effects in vitro (26)(27)(28)(29)(30) and in vivo (31,32). In PC, ITCs modulate epigenetic changes, induce the arrest of the cell cycle, activate apoptosis pathways and increase chemotherapeutic agent sensitivity; leading to the inhibition of cell proliferation, progression and invasionmetastasis (33).…”

Section: Introductionmentioning

confidence: 99%

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Effects of 3-butenyl isothiocyanate on phenotypically different prostate cancer cells

et al. 2018

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Isothiocyanates (ITCs) have gained increasing attention since they have been attributed the merits for the potential beneficial effects of cruciferous vegetable dietary consumption on cancer. The aim of the present study was to determine the cytotoxic effects of 3-butenyl ITC (3-BI) on prostate cancer (PC) cells under in vitro conditions. Two androgen-insensitive human PC cell lines, PC-3 and DU145, were assayed. Cells were cultured in the presence of increasing concentrations of 3-BI (5, 10, 30 and 50 µM) in the absence or presence of the chemotherapeutic drug docetaxel (DOCE) (1 and 2 nM). The cytotoxic effects of these compounds were analyzed using the trypan blue exclusion assay at 24, 48 and 72 h. Apoptosis and migration assays were also performed. The results showed that 3-BI induced a dose-dependent cytotoxic effect on PC-3 cells at 24, 48 and 72 h. These effects were significantly higher than those found with DOCE at 72 h of culture. Moreover, 3-BI also potentiated the effects of DOCE in a dose-dependent manner. Additionally, 3-BI showed inhibition of the migration of PC-3 cells. Nevertheless, 3-BI was not effective in the DU145 PC cell line. These results show a promising role for the 3-BI compound as a co-adjuvant agent in DOCE-based therapy in certain types of PC.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Effects of 3-butenyl isothiocyanate on phenotypically different prostate cancer cells

et al. 2018

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“…The two isothiocyanates occur with similar abundance to one another and in comparisons with broccoli sprouts for bioactivity, radish sprouts are similarly potent. Also of interest is that radishes are mostly devoid of ESP and thus generate higher yields of isothiocyanate without special pretreatments …”

Section: Chemistry Bioavailability and Metabolism Of Cruciferous Vementioning

confidence: 99%

Cruciferous Vegetables, Isothiocyanates, and Bladder Cancer Prevention

Abbaoui

Lucas

Riedl

et al. 2018

Molecular Nutrition Food Res

123

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Bladder cancer is a significant health burden due to its high prevalence, risk of mortality, morbidity, and high cost of medical care. Epidemiologic evidence suggests that diets rich in cruciferous vegetables, particularly broccoli, are associated with lower bladder cancer risk. Phytochemicals in cruciferous vegetables, such as glucosinolates, which are enzymatically hydrolyzed to bioactive isothiocyanates, are possible mediators of an anticancer effect. In vitro studies have shown inhibition of bladder cancer cell lines, cell cycle arrest, and induction of apoptosis by these isothiocyanates, in particular sulforaphane and erucin. Although not yet completely understood, many mechanisms of anticancer activity at the steps of cancer initiation, promotion, and progression have been attributed to these isothiocyanates. They target multiple pathways including the adaptive stress response, phase I/II enzyme modulation, pro-growth, pro-survival, pro-inflammatory signaling, angiogenesis, and even epigenetic modulation. Multiple in vivo studies have shown the bioavailability of isothiocyanates and their antitumoral effects. Although human studies are limited, they support oral bioavailability with reasonable plasma and urine concentrations achieved. Overall, both cell and animal studies support a potential role for isothiocyanates in bladder cancer prevention and treatment. Future studies are necessary to examine clinically relevant outcomes and define guidelines on ameliorating the bladder cancer burden.

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“…PEITC proved positive in micronucleus induction assays with human‐derived HepG2 cells and in chromosomal aberration or sister chromatid exchange tests with Chinese hamster ovary cell lines in vitro (Musk et al, ; Kassie and Knasmuller, ). Recently, we revealed that treatment with PEITC for 3 days at doses of 90 mg kg −1 body weight by gavage to rats caused no increase in the parameters of the comet assay in the urinary bladder and micronucleus assays in the bone marrow (Suzuki et al, ). Additionally, excessive doses of BITC did not induce DNA damage in the rat urinary bladder or liver in in vivo comet assays (Wada et al, ).…”

Section: Discussionmentioning

confidence: 99%

Horseradish extract promotes urinary bladder carcinogenesis when administered to F344 rats in drinking water

Cho

Hasumura

Imai³

et al. 2017

J of Applied Toxicology

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Horseradish extract (HRE), consisting mainly of a mixture of allyl isothiocyanate and other isothiocyanates, has been used as a food additive. To evaluate the potential hazards of HRE, a 104-week chronic study, a 2-week analysis of cell proliferation in the urinary bladder and a medium-term promotion bioassay of HRE were conducted with administration at concentrations of up to 0.04% HRE in the drinking water to male F344 rats. In the 104-week chronic study with 32 male rats per group, no treatment-related increases in the incidences of neoplastic lesions in any organ, including urinary bladder, were observed, except for simple hyperplasia in the urinary bladder in rats treated with HRE at concentrations of more than 0.01% (5.0 mg kg body weight day ). In the promotion study, HRE treatment after N-butyl-N-(4-hydroxybutyl)nitrosamine initiation caused a clear increase in papillary or nodular hyperplasia, papilloma, and urothelial carcinoma of the urinary bladder in the groups given HRE for 13 weeks at doses higher than 0.005%, 0.01%, and 0.04% (2.7, 5.4 and 20.5 mg kg body weight day ), respectively. In the 2-week cell proliferation analysis, treatment with HRE at concentrations greater than 0.005% (3.9 mg kg body weight day ) caused transient increases in 5-bromo-2'-deoxyuridine labeling indices in the urothelium. Although clear tumor induction was not observed, administration of relatively low-dose HRE increased cell proliferation in the urothelium and exerted obvious promoting effects on rat urinary bladder carcinogenesis. Further studies are needed to elucidate the mode of action of HRE in the rat urinary bladder to facilitate data extrapolation from the present study and provide insights into risk assessment. Copyright © 2017 John Wiley & Sons, Ltd.

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Toxic effects of 4‐methylthio‐3‐butenyl isothiocyanate (Raphasatin) in the rat urinary bladder without genotoxicity

Cited by 11 publications

References 29 publications

Effects of 3-butenyl isothiocyanate on phenotypically different prostate cancer cells

Effects of 3-butenyl isothiocyanate on phenotypically different prostate cancer cells

Cruciferous Vegetables, Isothiocyanates, and Bladder Cancer Prevention

Horseradish extract promotes urinary bladder carcinogenesis when administered to F344 rats in drinking water

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