Mechanism of enhancement of esophageal tumorigenesis by 6-phenylhexyl isothiocyanate

Morse, Mark A.; Lu, Jerry; Gopalakrishnan, Rajaram; Peterson, Lisa A.; Wani, Gulzar; Stoner, Gary D.

doi:10.1016/s0304-3835(96)04556-9

Cited by 25 publications

(11 citation statements)

References 20 publications

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“…As in previous studies (31), NMBA was 75% metabolized by untreated esophageal explants. Formation of benzoic acid, the major metabolite of NMBA in esophageal tissue, was consistent with changes in NMBA metabolism.…”

Section: Discussionsupporting

confidence: 84%

“…Explant cultures were prepared as described earlier (31). Briefly, individual esophagi were opened longitudinally and cut into small explants of approximately 3 mm.…”

Section: Nmba Metabolism In Esophageal Explant Culturesmentioning

confidence: 99%

“…The explants were then placed in an incubation chamber gassed with a mixture of 50% O 2 , 45% N 2 , and 5% CO 2 and maintained at 37°C with gentle rocking to allow the culture to be bathed inmedium and exposed alternately to the O 2 in the chamber. After 4 h of incubation, 500 µl of medium was collected from each explant culture and filtered through an Acrodisc (0.2-µm pore size; Gilman Sciences, Ann Arbor, MI) and analyzed for unmetabolized [ 3 H]NMBA and metabolites of NMBA by reverse-phase high-performance liquid chromatography (HPLC) as described earlier (25,31). The HPLC system used for these analyses consisted of a gradient controller, two 510 pumps, a C18 column, a 484 UV detector, an Eppendorf column heater (all from Millipore Corp., Bedford, MA), and a β-Ram radioflow detector (IN/US Systems, Inc., Tampa, FL).…”

Section: Nmba Metabolism In Esophageal Explant Culturesmentioning

confidence: 99%

“…Detection of eluates was by UV absorption at 254 nm and flow-through radioactivity. Major peaks of radioactivity were tagged, and the area under each peak was expressed as a percent of total radioactivity in the 50-µl sample (31). The results from three independent culture experiments were averaged.…”

Section: Nmba Metabolism In Esophageal Explant Culturesmentioning

confidence: 99%

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Modulation of N-Nitrosomethylbenzylamine Metabolism by Black Raspberries in the Esophagus and Liver of Fischer 344 Rats

Reen¹,

Nines²,

Stoner³

2006

Nutrition and Cancer

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Dietary freeze-dried black raspberries (BRBs) inhibit N-nitrosomethylbenzylamine (NMBA)-induced tumorigenesis in the Fischer 344 rat esophagus. To determine the mechanistic basis of the anti-initiating effects of BRBs, NMBA metabolism was studied in esophageal explant cultures and in liver microsomes taken from rats fed with AIN-76A diet or AIN-76A diet containing 5% or 10% BRBs. Five percent and 10% dietary BRBs inhibited NMBA metabolism in explants (26% and20%) and in microsomes (22% and28%), but the inhibition was not dose dependent. To identify active inhibitory component(s) in BRBs, esophageal explants and liver microsomes from control rats were treated in vitro with an ethanol extract of BRBs or with individual components of BRBs [ellagic acid (EA) and two anthocyanins (cyanidin-3-glucoside and cyanidin-3-rutinoside)]. NMBA metabolism in explants was inhibited maximally by cyanidin-3-rutinoside (47%) followed by EA (33%), cyanidin-3-glucoside (23%),and the extract (11%). Similarly, in liver microsomes, the inhibition was maximal by cyanidin-3-rutinoside (47%) followed by EA (33%) and cyanidin-3-glucoside (32%). Phenylethylisothiocyanate (PEITC), a potent inhibitor of NMBA tumorigenesis in rat esophagus, was a stronger inhibitor of NMBA metabolism in vivo and in vitro than BRBs or their components. Dietary BRBs and PEITC induced glutathione S-transferase activity in the liver.

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Section: Discussionsupporting

confidence: 84%

“…Explant cultures were prepared as described earlier (31). Briefly, individual esophagi were opened longitudinally and cut into small explants of approximately 3 mm.…”

Section: Nmba Metabolism In Esophageal Explant Culturesmentioning

confidence: 99%

Section: Nmba Metabolism In Esophageal Explant Culturesmentioning

confidence: 99%

Section: Nmba Metabolism In Esophageal Explant Culturesmentioning

confidence: 99%

See 2 more Smart Citations

Modulation of N-Nitrosomethylbenzylamine Metabolism by Black Raspberries in the Esophagus and Liver of Fischer 344 Rats

Reen¹,

Nines²,

Stoner³

2006

Nutrition and Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

“…For example, PHITC was very potent in blocking NNK-induced lung carcinogenesis in A/J mice, but it did not prevent NNK-induced skin tumor formation in the same strains of mice [18] . In addition, PHITC enhanced azoxymethane-induced colon tumorigenesis and NMBAinduced esophageal carcinogenesis in rats [29][30][31] . This study demonstrated that the effects of PHITC on esophageal cell proliferation, esophageal metabolism and DNA repair did not account for the enhancement of NMBA-induced tumorigenicity by PHITC, and the mechanism mediating the enhanced tumorigenicity has not been elucidated.…”

Section: Anticarcinogenic Activity Experimental Tumorigenesis In Labomentioning

confidence: 99%

Are isothiocyanates potential anti-cancer drugs?

2009

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Isothiocyanates are naturally occurring small molecules that are formed from glucosinolate precursors of cruciferous vegetables. Many isothiocyanates, both natural and synthetic, display anticarcinogenic activity because they reduce activation of carcinogens and increase their detoxification. Recent studies show that they exhibit anti-tumor activity by affecting multiple pathways including apoptosis, MAPK signaling, oxidative stress, and cell cycle progression. This review summarizes the current knowledge on isothiocyanates and focuses on their role as potential anti-cancer agents.

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Glucosinolates and Isothiocyanates: Cancer Preventive Effects

Razis

Arumugam

Konsue

2017

Fruit and Vegetable Phytochemicals

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The anticarcinogenic bioactivity of various isothiocyanates (ITCs) has been demonstrated in various animal models such as rats, mice, and hamsters, and in different target tissues such as lung, esophagus, and forestomach. A major chemopreventive mechanism of ITCs involves suppression of reactive metabolite generation and, therefore, a decrease in DNA adducts formation. Many in vitro studies have reported the effects of ITCs on cell cycle modulation and proapoptotic effects through a number of targets, at different points of the pathways. A comparative study in human subjects showed that the hydrolysis of glucosinolates and the absorption of ITCs are greater following ingestion of raw brassica with active plant myrosinase than after consumption of the cooked plant with denatured myrosinase. Apoptosis is considered a vital component of the cellular mechanisms responsible for the maintenance of homeostasis in multicellular organisms. Understanding the pathways of associated proteins provides an insight into the induction of apoptosis by anticancer agents.

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Mechanism of enhancement of esophageal tumorigenesis by 6-phenylhexyl isothiocyanate

Cited by 25 publications

References 20 publications

Modulation of N-Nitrosomethylbenzylamine Metabolism by Black Raspberries in the Esophagus and Liver of Fischer 344 Rats

Modulation of N-Nitrosomethylbenzylamine Metabolism by Black Raspberries in the Esophagus and Liver of Fischer 344 Rats

Are isothiocyanates potential anti-cancer drugs?

Glucosinolates and Isothiocyanates: Cancer Preventive Effects

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