The chemopreventive role of 5-methoxypsoralen (5-MOP) in the human hepatocellular carcinoma (HCC) cell line was investigated by studying the regulation of proliferation and apoptosis in HCC (J5) cells. Morphological analysis, cell viability assay, DNA analysis and cell-cycle analysis suggest that there are at least three modes of the suppressive effects shown by 5-MOP: (a) kills J5 cells directly; (b) induces apoptosis by arresting J5 cells at the G2/M phase in the cell cycle; (c) induces apoptosis through an independent pathway with cell-cycle arrest at 24-72 h of exposure. Further immunoblot analysis demonstrated that inhibition of cyclin B1 by 5-MOP may play an important role in G2/M arrest of J5 cells and provides an additional way to prevent cells from entering the M phase and undergoing apoptosis. 5-MOP therefore appears to exert its anticarcinogenic properties by cytotoxic effect, inducing apoptosis and inhibiting proliferation in the human hepatocellular carcinoma cell line. (C) 2003 Elsevier Science Ltd. All rights reserved.