Influence of B Ring Structure on Cell Cycle Inhibitory Activities of Flavonols in a Human Oesophageal Adenocarcinoma Cell Line (OE33)

The effects of three structurally related flavonols (kaempferol, quercetin, myricetin) on anti-proliferation and cell cycle arrest in human oesophageal adenocarcinoma OE33 cells were determined and compared by MTT assay and flow cytometry analysis. The results showed that three flavonols not only inhibited proliferation but also induced G
₂
/M arrest in OE33 cells. Moreover, G
₂
/M arrest-inducing activity of quercetin (with two hydroxyl groups in the B ring) was better than that of kaempferol (with one hydroxyl group in the B ring) and myricetin (with three hydroxyl groups in the B ring). It was further corroborated by comparing G
₂
/M arrest-inducing activity of two flavones (apigenin and luteolin) whose B rings were same to kaempferol and quercetin, respectively. Additionally, the results of real-time RT-PCR and Western-blot analysis showed that the expressions of GADD45beta and 14-3-3sigma were upregulated but the expression of cyclin B1 was downregulated by flavonols at the mRNA and the protein levels. It is suggested that the influence of B ring structure on cell cycle inhibitory activities of flavonols might result from the regulatory expression of these genes at the mRNA and protein levels.