Chemopreventive effects of coumaperine from pepper on the initiation stage of chemical hepatocarcinogenesis in the rat.
This study was designed to investigate the chemopreventive action of three natural products, coumaperine, aurapten and an extract from rosemary, against the initiation stage of rat hepato-carcinogenesis. Coumaperine has been isolated from white pepper as a naturally occurring antioxidative agent, but its potential modifying effects on carcinogenesis remain unclear. In experiment 1, a modification of the model developed by Tsuda et al. was applied, with assessment of numbers and areas of induced glutathione S-transferase placental form (GST-P)-positive hepatocellular foci in male F344 rats. Coumaperine, aurapten and the extract from rosemary were administered i.g. at 100 mg / kg / day once daily for 5 days with initiation by diethylnitrosamine (DEN) on day 4 (20 mg / kg, i.p.). Numbers and areas of GST-P-positive foci in each group given test chemicals tended to be decreased as compared to the vehicle control group values, significance being achieved for number with coumaperine. Experiment 2 was planned to investigate the mechanism of the inhibitory effects of coumaperine. Livers at 8 h after initiation by DEN were examined with coumaperine administered at 100 mg / kg / day once daily for 3 days. Proliferating cell nuclear antigen (PCNA)-positive cells tended to be decreased as compared to the vehicle control, but no effects on apoptosis or cytochrome P-450 (CYP) 2E1 expression were apparent. Our results suggest that coumaperine provides protection against initiation of hepatocarcinogenesis, and that this is related to inhibition of cell proliferation.
First Department of Pathology, Osaka City University Medical School, Abeno-ku, Osaka 545-8585, Japan.
M
M
Kitano
H
H
Wanibuchi
H
H
Kikuzaki
N
N
Nakatani
S
S
Imaoka
Y
Y
Funae
S
S
Hayashi
S
S
Fukushima
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002273:Carcinogens; D002455:Cell Division / Q000187:drug effects; D003374:Coumarins / Q000627:therapeutic use; D004052:Diethylnitrosamine; D015870:Gene Expression; D005982:Glutathione Transferase / Q000378:metabolism; D007150:Immunohistochemistry; D019686:Lamiaceae / Q000737:chemistry; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009697:Nucleolus Organizer Region / Q000187:drug effects; D010880:Piperidines / Q000627:therapeutic use*; D010936:Plant Extracts / Q000627:therapeutic use; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D016622:Silver Staining; D017365:Spices
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D003374:Coumarins; D010880:Piperidines; D010936:Plant Extracts; D018809:Proliferating Cell Nuclear Antigen; D004052:Diethylnitrosamine; C412962:coumaperine; D005982:Glutathione Transferase; C105832:aurapten