Chemopreventive Effects of Coumaperine from Pepper on the Initiation Stage of Chemical Hepatocarcinogenesis in the Rat

Abstract

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 hepatocarcinogenesis. 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.

Anticancer Effects of Rosemary (Rosmarinus officinalis L.) Extract and Rosemary Extract Polyphenols

“…From this point, rats were fed a normal diet for 3 weeks until undergoing partial hepatectomy. Examination of liver tissue suggested RE may exert some protective antioxidant effects [44]. In accordance with this, use of Swiss mice exposed to 6 Grays (Gy) ionizing radiation (IR) in their liver once, followed by treatment with 1000 mg/kg RE fed orally, daily for 5 days suggested protective, antioxidant activity by RE.…”

“…Increases in glutathione (GSH), an antioxidant, and reductions in lipid peroxidase (LPx), an oxidizing agent resulting in free radical production and cell damage, have been recorded in IR-induced mouse liver [45] and DMBA-induced mouse skin cancer [46,47] models treated with RE. Similarly, RE decreased glutathione-S transferase (GST) positive foci, which are associated with oxidative damage from the reduction of GSH [40], in a rat DEN-induced liver cancer model however, results were not significant and should be taken with caution [44]. …”

Rapid analysis of gene expression changes caused by liver carcinogens and chemopreventive agents using a newly developed three‐dimensional microarray system

“…26) These compounds have inhibitory effects on rat colon carcinogenesis. Caffeic acid, 27) cathechol 27) and auraptene 28) have inhibitory effects on rat hepatocarcinogenesis. We treated rats with these chemicals for 2 weeks and performed gene expression analysis using a novel 3D-microarray system to assess the feasibility of establishing a bioassay system to predict carcinogenicity and chemopreventive activity of chemicals from effects on gene expression patterns.…”

Chemoprevention of Hepatocarcinogenesis with Dietary Isoprenic Derivatives: Cellular and Molecular Aspects

“…Inhibition of cell proliferation as observed through the reduction of PCNA was implicated in the chemopreventive action of this dietary agent [36]. In a DENAinitiated hepatocarcinogenesis study, coumaperine was shown to decrease the numbers of GST-P foci in male F344 rats.…”

“…Auraptene was initially investigated for its chemopreventive actions by Kitano and co-workers [36]. Auraptene was initially investigated for its chemopreventive actions by Kitano and co-workers [36].…”