Abstract
Phenethyl isothiocyanate (PEITC), the most comprehensively studied aromatic isothiocyanate, has been shown to act as an anti-cancer agent mainly through modulation of biotransformation enzymes responsible for metabolizing carcinogens in the human body. Humans are often exposed to carcinogenic factors, some of which through the diet, such as polycyclic aromatic hydrocarbon benzo[a]pyrene via the consumption of over-cooked meats. Inhibition of the enzymes responsible for the bioactivation of this carcinogen, for example CYP1A1, the major enzyme required for polycyclic aromatic hydrocarbons (PAHs) bioactivation, is recognized as a chemoprevention strategy. To evaluate the inhibitory effects of PEITC against benzo[a]pyrene-induced rise in rat liver CYP1A1 mRNA and apoprotein levels. Precision cut rat liver slices were treated with benzo[a]pyrene at 1 and 5 μM in the presence of PEITC (1-25 μM) for 24 hours, followed by determination of CYP1A1 mRNA and apoprotein levels using quantitative polymerase chain reaction and immunoblotting. Findings revealed that PEITC inhibited benzo[a]pyrene-induced rise in rat liver CYP1A1 mRNA in a dose-dependent manner as well as the apoprotein levels of CYP1A. It was demonstrated that PEITC can directly inhibit the bioactivation of benzo[a]pyrene, indicating chemopreventive potential.
Highlights
Human are exposed to chemical carcinogens almost on daily basis
CYP1A1 mRNA studies A 24-hour incubation of precision-cut rat liver slices with benzo[a]pyrene (1 and 5 μM) alone resulting in rises of CYP1A1 mRNA levels; this effect was inhibited in a concentration-dependent manner by Phenethyl isothiocyanate (PEITC) (Figure 1 and Figure 2)
Following the experimental evidence indicating modulation of carcinogen-metabolizing enzymes by PEITC in human and rat liver slices as well as in vivo in rat as described in the published articles (Ioannides and Konsue 2008, Konsue and Ioannides, 2010a, 2010b), the present study was conducted to elucidate the role of PEITC as chemopreventive agent towards distinct carcinogen namely benzo[a]pyrene
Summary
Human are exposed to chemical carcinogens almost on daily basis Major sources of these compounds are, for example, polycyclic aromatic hydrocarbon (PAH) derived from tobacco and cooked-food (Hecht, 2003), and other food-derived carcinogens such as heterocyclic amines (HCAs) and nitrosamines (Boyce et al, 2014). Inhibition of the enzymes responsible for the bioactivation of carcinogens such as CYP1A1 and 1A2, the major enzymes required for PAH and HCA bioactivation, respectively (Kobayashi et al, 2009; Wohak et al, 2014) is recognized as a chemoprevention strategy (Liu et al, 2013). Inhibition of the enzymes responsible for the bioactivation of this carcinogen, for example CYP1A1, the major enzyme required for polycyclic aromatic hydrocarbons (PAHs) bioactivation, is recognized as a chemoprevention strategy. Results: Findings revealed that PEITC inhibited benzo[a]pyrene-induced rise in rat liver CYP1A1 mRNA in a dose-dependent manner as well as the apoprotein levels of CYP1A. Conclusions: It was demonstrated that PEITC can directly inhibit the bioactivation of benzo[a]pyrene, indicating chemopreventive potential
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