OBJECTIVE: We aimed to evaluate the potential mediating roles of inflammatory, metabolic, liver injury, and iron metabolism biomarkers on the association between coffee intake and the primary form of liver cancer-hepatocellular carcinoma (HCC).

DESIGN: We conducted a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition among 125 incident HCC cases matched to 250 controls using an incidence-density sampling procedure. The association of coffee intake with HCC risk was evaluated by using multivariable-adjusted conditional logistic regression that accounted for smoking, alcohol consumption, hepatitis infection, and other established liver cancer risk factors. The mediating effects of 21 biomarkers were evaluated on the basis of percentage changes and associated 95% CIs in the estimated regression coefficients of models with and without adjustment for biomarkers individually and in combination.

RESULTS: The multivariable-adjusted RR of having ≥4 cups (600 mL) coffee/d compared with <2 cups (300 mL)/d was 0.25 (95% CI: 0.11, 0.62; P-trend = 0.006). A statistically significant attenuation of the association between coffee intake and HCC risk and thereby suspected mediation was confirmed for the inflammatory biomarker IL-6 and for the biomarkers of hepatocellular injury glutamate dehydrogenase, alanine aminotransferase, aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), and total bilirubin, which-in combination-attenuated the regression coefficients by 72% (95% CI: 7%, 239%). Of the investigated biomarkers, IL-6, AST, and GGT produced the highest change in the regression coefficients: 40%, 56%, and 60%, respectively.

METHODS: Male Wistar rats (200-250 g) were divided into 4 groups according to the diet given: control group (normal diet), ChV group with three different doses (50, 150 and 300 mg/kg body weight), liver cancer- induced group (choline deficient diet + 0.1% ethionine in drinking water or CDE group), and the treatment group (CDE group treated with three different doses of ChV). Rats were killed at 0, 4, 8 and 12 weeks of experiment and blood and tissue samples were taken from all groups for the determination of tumour markers expression alpha-fetoprotein (AFP), transforming growth factor-β (TGF-β), M2-pyruvate kinase (M2-PK) and specific antigen for oval cells (OV-6).

RESULTS: Serum level of TGF-β increased significantly (p < 0.05) in CDE rats. However, ChV at all doses managed to decrease (p < 0.05) its levels to control values. Expressions of liver tumour markers AFP, TGF-β, M2-PK and OV-6 were significantly higher (p < 0.05) in tissues of CDE rats when compared to control showing an increased number of cancer cells during hepatocarcinogenesis. ChV at all doses reduced their expressions significantly (p < 0.05).

AIM OF THE STUDY: In this study, the effects of F3, lutein and β-sitosterol on tumor development and metastasis were investigated in 4T1-induced mouse mammary carcinoma model.

MATERIALS AND METHODS: Tumor-bearing mice were fed with F3 (100 mg/kg/day), lutein (50 mg/kg/day) and β-sitosterol (50 mg/kg/day) for 30 days (n = 5 each group). Tumor physical growth parameters, animal body weight and development of secondary tumors were investigated. The safety profile of F3 was assessed using hematological and histomorphological changes on the major organs in normal control mice (NM).

RESULTS: Our findings revealed significant reduction of physical tumor growth parameters in all tumor-bearing mice treated with F3 (TM-F3), lutein (TM-L) or β-sitosterol (TM-β) as compared with the untreated group (TM). Statistically significant reduction in body weight was observed in TM compared to the NM or treated (TM-F3, TM-L and TM-β) groups. Histomorphological examination of tissue sections from the F3-treated group showed normal features of the vital organs (i.e., liver, kidneys, lungs and spleen) which were similar to those of NM. Administration of F3 to NM mice (NM-F3) did not cause significant changes in full blood count values.