The molecular mechanisms of wogonin-induced apoptosis of human hepatoma SMMC-7721 cells are reported. Wogonin treatment resulted in significant inhibition of SMMC-7721 cells in a time-dependent and concentration-dependent manner. Typical morphological changes and apoptotic blebbing in SMMC-7721 cells were observed after treatment with 1x10(-4) mol/l wogonin for a period of 0-48 h. Flow cytometry and Annexin-V/propidium iodide double-staining experiments revealed a dramatic increase in the number of apoptotic and G0/G1 phase cells after wogonin treatment. The proapoptotic activity of wogonin is attributed to its ability to modulate the expression of bcl-2 and bax proteins. It is observed that the expression of bax protein is dramatically increased whereas the synthesis of bc1-2 protein is significantly decreased when cells are treated with wogonin. The results presented in this paper suggested an important relationship between gene regulation and wogonin-induced apoptosis, and indicated the possibility of developing naturally occurring monoflavonoids as novel anticancer agents for better management of human cancers.