Suppressive effects of caraway (Carum carvi) extracts on 2, 3, 7, 8-tetrachloro-dibenzo-p-dioxin-dependent gene expression of cytochrome P450 1A1 in the rat H4IIE cells.
Cytochrome P450 1A1 (CYP1A1) is among the cytochrome P450 classes known to convert xenobiotics and endogenous compounds to toxic and/or carcinogenic metabolites. Suppression of CYP1A1 over expression by certain compounds is implicated in prevention of cancer caused by chemical carcinogens. Chemopreventive agents containing high levels of flavonoids and steroids-like compounds are known to suppress CYP1A1. This study was carried out for assessment of the genomic and proteomic effects of caraway (Carum carvi) extracts containing high levels of both flavonoids and steroid-like substances on ethoxy resorufin dealkylation (EROD) activity and CYP1A1 at mRNA levels. Rat hepatoma cells co-treated with a CYP1A1 inducer i.e. TCDD (2, 3, 7, 8-tetrachlorodibenzo-p-dioxin) and different preparations of caraway extracts at concentrations of 0, 0.13, 1.3, and 13 microM in culture medium. After incubation (37 degrees C and 7% CO2 for 20 h), changes in EROD specific activity recorded and compared in cells under different treatments. The results show that caraway seed extract prepared in three different organic solvents suppressed the enzyme activity in hepatoma cells in a dose-dependent manner. The extracts added above 0.13 microM could significantly inhibit EROD activity and higher levels of each extract (1.3 and 13 microM) caused approximately 10-fold suppression in the enzyme activity. Accordingly, data obtained from the RT-PCR (TaqMan) clearly showed the suppressive effects of plant extract on CYP1A1-related mRNA expression. These data clearly show that substances in caraway seeds extractable in organic solvents can potentially reverse the TCDD-dependent induction in cytochrome P450 1A1.
Naderi-Kalali
B
B
Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modarres University, P.O. Box 14115-111, Tehran, Iran.
Allameh
A
A
Rasaee
M J
MJ
Bach
H-J
HJ
Behechti
A
A
Doods
K
K
Kettrup
A
A
Schramm
K-W
KW
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000201:enzymology*; D029974:Carum / Q000737:chemistry*; D045744:Cell Line, Tumor; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004785:Environmental Pollutants / Q000633:toxicity; D004790:Enzyme Induction / Q000187:drug effects / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D008113:Liver Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D010936:Plant Extracts / Q000494:pharmacology; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats
D004785:Environmental Pollutants; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D019363:Cytochrome P-450 CYP1A1