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 200μM after 48h 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 200μM at 48h 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 bax and bcl2 transcription. Results of the currents study suggest that among the citrus
flavonoids, double bond between C2 and C3 and
hydroxyl group at C3, C6 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.