Inhibition of cyclooxygenase-2 activity in head and neck cancer cells by genistein.

Genistein, rich in soybean, has been reported to have anti-cancer activity on several cancers. However, the molecular mechanism of its anti-cancer activity still remains unclear. We investigated the effect of genistein on a human oral squamous carcinoma line (SCC-25), and demonstrated that genistein inhibited SCC-25 cell growth via G2/M phase arrest. We observed a significant decrease of proliferating cell nuclear antigen expression in these cells after treatment, but no significant change in the number of apoptotic cells, indicating that the major action of genistein is inhibition of cancer cell proliferation. We also observed a high level of prostaglandin E2 (PGE2) in these cells and PGE2 synthesis in SCC-25 cells was significantly suppressed by genistein. We demonstrated that genistein directly inhibited cycloxygenase-2 (COX-2) activity, an inducible enzyme that converts arachidonic acid to prostaglandins, similar to the action of celecoxib, a selective COX-2 inhibitor. However, the anticancer activity of genistein was much weaker than that of indomethacin (non-selective COX inhibitor), celecoxib and baicalein (flavonoid isolated from Scutellaria baicalensis). These results suggested that genistein might be useful as a chemopreventive agent rather than a chemotherapeutic agent.