Huanglian, a Chinese herbal extract, inhibits cell growth by suppressing the expression of cyclin B1 and inhibiting CDC2 kinase activity in human cancer cells

Huanglian is an herb that is widely used in China for the treatment of gast roenteritis. We elected to determine whether huanglian could inhibit tumor cell growth by modulating molecular events directly associated with the cel l cycle. Huanglian inhibited tumor growth and colony formation of gastric, colon, and breast cancer cell lines in a time- and dose-dependent manner. C ell growth was completely inhibited after 3 days of continuous drug exposur e to 10 mug/ml of herb. This degree of growth inhibition was significantly greater than that observed with berberine, the major constituent of the her b. The inhibition of cell growth by huanglian was associated with up to 8-f old suppression of cyclin B1 protein. This resulted in complete inhibition of cdc2 kinase activity and accumulation of cells in G(2). The mRNA express ion of cyclin B1 was not changed after huanglian treatment. There was no ch ange in the protein expression of cyclins A or E. Therefore, the effect of huanglian on inhibiting tumor growth seems to be mediated by the selective suppression of cyclin B1, which results in the inhibition of cdc2 kinase ac tivity. Inhibition of cyclin dependent kinase (cdk) activity is emerging as an attractive target for cancer chemotherapy. Huanglian represents a class of agents that can inhibit tumor cell growth by directly suppressing the e xpression of a cyclin subunit that is critical for cell cycle progression. These results indicate that traditional Chinese herbs may represent a new s ource of agents designed for selective inhibition of cyclin dependent kinas es in cancer therapy.