Flavonoids uptake and their effect on cell cycle of human colon adenocarcinoma cells (Caco2)

Abstract

Green tea, mainly through its constituents epigallocatechin gallate, epigallocatechin, epicatechin gallate and epicatechin, has demonstrated anticarcinogenic activity in several animal models, including those for skin, lung and gastro-intestinal tract cancer, although less is known about colorectal cancer. Quercetin, the major flavonoid present in vegetables and fruit, exerts potential anticarcinogenic effects in animal models and cell cultures, but less is known about quercetin glucosides. The objectives of this study were to investigate (i) the antioxidant activity of the phenolic compounds epicatechin, epigallocatechin gallate, gallic acid and quercetin-3-glucoside; (ii) the cytotoxicity of different concentrations of epicatechin, epigallocatechin gallate, and gallic acid; (iii) the cellular uptake of epicatechin, epigallocatechin gallate, gallic acid and quercetin-3-glucoside and (iv) their effect on the cell cycle. Human colon adenocarcinoma cells were used as experimental model. The results of this study indicate that all dietary flavonoids studied (epicatechin, epigallocatechin gallate, gallic acid and quercetin-3-glucoside) show a significant antioxidant effect in a chemical model system, but only epigallocatechin gallate or gallic acid are able to interfere with the cell cycle in Caco2 cell lines. These data suggest that the antioxidant activity of flavonoids is not related to the inhibition of cellular growth. From a structural point of view, the galloyl moiety appears to be required for both the antioxidant and the antiproliferative effects. Epidemiological studies from around the world have consistently reported that a high intake of fruit and vegetables is associated with a low incidence of most types of cancer (Wang et al, 1989;Dragsted et al, 1993). It is estimated that about 70% of all cancers are attributable to the diet. Colorectal cancer is the second most prevalent cancer in the developed world (Parkin et al, 1985). Western diet with a high intake of calories from fat and low fibre supply has been linked to an increase of colon cancer incidence, whilst vegetarian or mediterranean diets are more protective (Vargas and Alberts, 1992). Several compounds have been identified in plants which have well recognised antioxidant properties, such as carotenoids, ascorbic acid, a-tocopherol and flavonoids (Block et al, 1992;Hertog et al, 1992) and inhibit cancer development.Thus, the use of natural substances, that are derived from the diet for chemoprevention, might provide a strategy to inhibit the development of cancer. Green tea, mainly through its constituents epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin gallate (ECG) and epicatechin (EC), has demonstrated anticarcinogenic activity in several animal models, including those for skin, lung and gastro-intestinal tract cancer (Katiyar et al, 1992;Yang and Wang, 1993). Several recent studies (Berger et al, 2001;Uesato et al, 2001) on the effect of green tea polyphenolics on colon cancer cell lines have shown antiproliferative acti...

Review of anticancer mechanisms of isoquercitin

“…They concluded that IQ is a promising antioxidant agent but that it did not inhibit Caco2 cellular growth [79] . In 2005, Kern et al [80] reported a perspective on the antiproliferative effect and demonstrated the potent EGFRinhibitory properties of polyphenolrich apple juice extract in adenocarcinoma colon in vitro model (HT29) [80] .…”

“…In 2002, Salucci et al [79] suggested that the antioxidant activity of flavonoids was not involved in their inhibition of the growth of colon adenocarcinoma cells (Caco2). They concluded that IQ is a promising antioxidant agent but that it did not inhibit Caco2 cellular growth [79] .…”

Anticancer and Antioxidant Activities of Some Algae from Western Libyan Coast

“…Therefore, the cytotoxic effect of algae, via the inhibition of the proliferation of Caco2 cells is likely to be related to their content of these compounds especially polyphenolics and flavonoids [39]. For example, quercetin shows antioxidant activity that is believed to have a cytoprotective role against oxidative stress [40].…”

Induction of cancer-specific cytotoxicity towards human prostate and skin cells using quercetin and ultrasound

“…Quercetin, a major bioflavonoid in human diet, has been identified as a chemotherapeutic agent for the treatment of breast cancer (Singhal et al, 1995;Choi et al, 2001), colon cancer (Salucci et al, 2002), ovarian cancer (Chan et al, 2003) and prostate cancer (Knowles et al, 2000;Nakanoma et al, 2001;Kobayashi et al, 2002). Antiproliferative action of quercetin is hypothesised to be mediated by attenuating phosphorylation of activated hsp transcription factor (hsf), shortly after its trimerisation (Nagai et al, 1995;Lee et al, 1998), thereby resulting in increased susceptibility of hsf to proteolytic degradation and as a consequence inhibiting all downstream events, including hsp expression (Li et al, 1999).…”