Disease relevance of isothiocyanatomethylbenzene

• Additions of benzyl isothiocyanate or phenethyl isothiocyanate to a diet containing CMBA inhibited formation of neoplasms of the forestomach and pulmonary adenomas in female ICR/Ha mice [1].
• It is now shown that DIM, ICZ, SUL, and BITC can each stimulate apoptosis in human colon adenocarcinoma LS-174 and Caco-2 cells [2].
• Cell cycle arrest, apoptosis induction and inhibition of nuclear factor kappa B activation in anti-proliferative activity of benzyl isothiocyanate against human pancreatic cancer cells [3].
• The potent inhibition of P450 2A6- and 2A13-mediated metabolisms together with the ability of BITC and PEITC to inactivate the enzymes suggests the possibility that these isothiocyanates could be developed as chemopreventive agents to protect smokers who are unwilling or unable to quit smoking against lung cancer [4].
• Here, we studied the antitumor effects of benzyl isothiocyanate (BITC; Ph-CH2-N=C=S), the predominant ITC compound in broccoli, on head and neck squamous cell carcinoma (HNSCC) cell lines [5].

High impact information on isothiocyanatomethylbenzene

• Diets containing 0.5% bisethylxanthogen or 0.5% benzylisothiocyanate also elevated microsomal DT-diaphorase specific activities in several organs [6].
• In the present study, we clarified the molecular mechanism underlying the relationship between benzyl isothiocyanate (BITC)-induced cell cycle arrest and apoptosis and the involvement of mitogen-activated protein kinases (MAPKs) [7].
• A link between benzyl isothiocyanate-induced cell cycle arrest and apoptosis: involvement of mitogen-activated protein kinases in the Bcl-2 phosphorylation [7].
• This study provides evidence for the existence of a novel xenobiotic substrate site in hGST P1-1, which can be occupied by benzyl isothiocyanate and is distinct from that of monobromobimane and 1-chloro-2,4 dinitrobenzene [8].
• In the present study, we studied the molecular mechanism underlying cell death induced by a cancer chemoprotective compound benzyl isothiocyanate (BITC) [9].

Chemical compound and disease context of isothiocyanatomethylbenzene

• Male 6-week-old Syrian hamsters were subcutaneously injected with 10mg/kg body weight N-nitrosobis(2-oxopropyl)amine (BOP) four times within a week, and fed a diet supplemented with 80ppm benzyl isothiocyanate (BITC), 80ppm sulforaphane (SFN) or 10ppm resveratrol (RES) during the initiation or post-initiation stages [10].
• Exposure to AITC and BITC at 2.8 mg/kg body weight, and the same mol quantity (37 micromol/kg) of BITC-metabolites was for 2 h [11].

Biological context of isothiocyanatomethylbenzene

• We measured GSH, GSSG, cell volume, and cell pH, and we used the Nernst equation to determine the changes in redox potential Eh of the 2GSH/GSSG pool in response to the differentiating agent, sodium butyrate, and the detoxification enzyme inducer, benzyl isothiocyanate [12].
• Furthermore, all four isothiocyanates extensively inhibited NNK oxidation in rat lung and nasal mucosa microsomes as well as mouse lung microsomes in vitro, with PEITC (IC50 of 120-300 nM) being more potent than BITC (IC50 of 500-1400 nM) but less potent than PBITC and PHITC (IC50 of 15-180 nM) [13].
• Benzyl isothiocyanate (BITC) treatment down-regulates cyclins and CDKs and up-regulates the expression of the CDK inhibitor p21, but up-regulation of p27 or p53 was not detected [14].
• Benzyl isothiocyanate-induced DNA damage causes g2/m cell cycle arrest and apoptosis in human pancreatic cancer cells [15].
• In this study, the kinetics for the inactivation of cytochrome P450 2E1 by benzyl isothiocyanate (BITC) were elucidated [16].

Anatomical context of isothiocyanatomethylbenzene

• A novel function of benzyl isothiocyanate in vascular smooth muscle cells: the role of ERK1/2, cell cycle regulation, and matrix metalloproteinase-9 [14].
• Benzyl isothiocyanate inhibits excessive superoxide generation in inflammatory leukocytes: implication for prevention against inflammation-related carcinogenesis [17].
• The effects of benzyl isothiocyanate (BITC) and benzyl thiocyanate (BTC) on two types of DNA synthesis were examined in hepatocyte primary cultures (HPC) [18].
• Similarly, at a single dose of 0.25 mmol/kg (5 mumol/mouse) 24 h before death, PEITC, PBITC, PHITC but not BITC, decreased NNK oxidation in mouse lung microsomes by 40-85%, with PBITC and PHITC showing greater inhibition [13].
• 2. The non-enzymic reaction of GSH with benzyl isothiocyanate was rapid and was catalysed by rat liver cytosol [19].

Associations of isothiocyanatomethylbenzene with other chemical compounds

• Both BITC and PEITC were able to inactivate P450 2A6 and 2A13 in an NADPH-dependent manner potentially through the formation of adducts to the apoprotein [4].
• Modifying effects of benzyl isothiocyanate and benzyl thiocyanate on DNA synthesis in primary cultures of rat hepatocytes [18].
• Conjugates formed by reaction of monoclonal antibody B72.3 with benzyl isothiocyanate derivatives of four amino polycarboxylate chelators (NTA, EGTA, EDTA, DTPA) were labeled with indium-111 and administered iv to athymic mice bearing antigen-positive (LS174T) and antigen-negative (A375) human tumor xenografts [20].
• The standard inducer tert-butylhydroquinone (tBHQ), the electrophile benzyl isothiocyanate (BITC), and the antioxidant flavonoid quercetin were found to induce luciferase expression, thereby validating these newly developed reporter cell lines [21].
• Influence of benzylisothiocyanate and 13-cis-retinoic acid on micronucleus formation induced by benzo[a]pyrene [22].

Gene context of isothiocyanatomethylbenzene

• Metyrapone, xanthate C8, and benzylisothiocyanate inhibited several other cytochrome P450 activities rather effectively, some of them even more potently than CYP2B6, and consequently are unsuitable as CYP2B6-selective probes [23].
• Benzyl isothiocyanate-induced apoptosis in human breast cancer cells is initiated by reactive oxygen species and regulated by Bax and Bak [24].
• Requirement of a carbon spacer in benzyl isothiocyanate-mediated cytotoxicity and MAPK activation in head and neck squamous cell carcinoma [5].
• Benzyl isothiocyanate (BITC), present in cruciferous vegetables, is an efficient substrate of human glutathione S-transferase P1-1 (hGST P1-1) [8].
• Inactivation of cytochrome P450 2E1 by benzyl isothiocyanate [16].

Analytical, diagnostic and therapeutic context of isothiocyanatomethylbenzene

• Benzyl isothiocyanate (BITC), a cruciferous vegetable-derived compound, has been shown to inhibit chemically induced cancer in animal models [3].
• Benzyl-isothiocyanate (BITC) was identified as one component of onion lipids by combined gas chromatography/mass spectrometry [25].
• The two glucosinolates were semiquantified by HPLC, and benzylisothiocyanate was semiquantified by GC/MS [26].
• We thus conclude that at high concentration, EEPS is capable of causing irreversible uterine tocolysis probably due to the damaging effect of BITC (its chief phytochemical) on the myometrium [27].
• Pregnancy outcomes following pre- and post-implantation exposure of Sprague-Dawley rats to benzyl isothiocyanate [28].

References