Summarywe have already reported that instant coffee powder (ICP) and ICP4oaded rat sera could suppress proliferation and invasion of rat ascites hepatoma cell line of AH109A in vitro. In this report, we examined the mechanisms for suppression of tumor cell prolifer ation and invasion by ICP, and the effect of ICP on in vivo tumor growth, metastasis and abnormal lipoprotein profiles in hepatoma-bearing rats. ICP, when directly added to the cuh ture media, induced cell cycle arrest (elongation of S phase) at a lower concentration (0.3 mg/mL) and apoptosis at a higher concentration (0.6-1.2mg/mL). ICP and ICP-loaded rat sera showed reactive oxygen species (OS)-scavenging property and canceled the enhance ment of invasive activity of hepatoma cells induced by OS in vitro. These results suggest that ICP suppresses the proliferation by inducing cell cycle arrest and apoptosis, and the invasion by scavenging ROS and that ICP could retain these properties after their gas trointestinal absorption. The hepatoma-bearing rats were fed with a 20% casein diet (20C) or 20C supplemented with 0.1% ICP for 14 d. Dietary ICP significantly reduced solid tumor growth and tended to reduce hepatoma metastases to lung and lymphatic nodes, suggesting that ICP could suppress tumor cell proliferation and invasion in vivo. In addition, dietary ICP significantly increased serum high density lipoprotein (HDL)-cholesterol and tended to reduce very low-density and low-density lipoprotein (ULDL+LDL)-cholesterol, resulting in amelioration of abnormal lipoprotein profiles occurred in hepatoma-bearing rats. In conclu sion, ICP has the ability to induce cell cycle arrest and apoptosis in hepatoma cells and to suppress tumor cell invasion by reducing oxidative stresses in vitro, and it could also exhibit these effects in vivo, leading to the inhibition of tumor growth and metastases.
Actions of chlorogenic acid, a major component of coffee, andits constituents, caffeic and quinic acids, on theproliferation and invasion of AH109A, a rat ascites hepatomacell line, were investigated using in vitro assay systems. Allthree components suppressed the AH109A invasion atconcentrations of 5-40 muM without altering the cellproliferation. At the concentration of 10 muM, chlorogenic,caffeic and quinic acids significantly (P < 0.05) suppressedthe invasion by 68%, 36% and 31%, respectively, implying thatthe suppressive effect of chlorogenic acid on the AH109Ainvasion might result from the additive effects of itsconstituents, caffeic and quinic acids. At the concentrationof 10 muM, cinnamic acid and p-coumaric acid (4-hydroxycinnamicacid) exerted no or little influence on the invasion, whereascaffeic acid (3,4-dihydroxycinnamic acid) significantly (P <0.05) suppressed it, suggesting the possible involvement ofthe 3,4-dihydroxy group of caffeic acid in the suppression.Chlorogenic acid was thus demonstrated to be one of thechemical entities in coffee suppressing the hepatoma invasionin vitro, and both of its constituents, caffeic and quinicacids, to be responsible for the anti-invasive activity. Theseresults suggest the existence of nutritionally andpharmacologically important substances in coffee which controltumor cell invasion.
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