Differential inhibition of human colon cancer cells by structurally similar flavonoids of citrus

A number of studies in the recent years have evaluated the anti-proliferative activity of flavonoids. Although certain studies investigated the structure-activity based on the phenotypic assays, no study has correlated the flavonoids structure with the ability to alter gene/protein expression. Present study was focused to understand the structure-function relationship of citrus flavonoids in terms of their ability to alter the gene expression in the colon adenocarcinoma cells. Eight structurally related flavonoids found in citrus were evaluated for their ability to inhibit colon cancer (SW480) cells, as well as change the expression of apoptosis related genes/proteins. Apigenin and quercetagetin demonstrated most significant inhibition of cell proliferation with 63.6% and 45.7% inhibition of cell growth at 200 mu M after 48 h of incubation, respectively. The cell death was also confirmed by images of fluorescently tagged cells. Furthermore, up-regulation of Bax/Bcl2 protein ratio as well as activation of Caspase3 at 200 mu M at 48 h confirmed the induction of apoptosis by apigenin and quercetagetin. In addition, results suggest that the change in Bax/Bcl2 ratio by apigenin and quercetagetin seems to be due to their ability to alter the expression of box and bcl2 transcription. Results of the currents study suggest that among the citrus flavonoids, double bond between C-2 and C-3 and hydroxyl group at C-3, C-6 are highly decisive for the proliferation inhibition and apoptosis induction ability. Taken together, these results demonstrate that among the major flavonoids of citrus, apigenin and quercetagetin have potent anti-cancer activity through inducing apoptosis in SW480 human colon cancer cells. (C) 2011 Elsevier Ltd. All rights reserved.