The sensitivity of human hepatoma (HepG2) and oral squamous cell carcinoma (HSC-2) cell lines against various apoptosis-inducing agents was compared. HepG2 cells were generally more resistant to an oxidant (H2O2), antioxidants (sodium ascorbate, gallic acid, epigallocatechin gallate) and anticancer drugs (doxorubicin, methotrexate, cisplatin (CDDP), etoposide, 5-fluoro-2,4(1H,3H)-pyrimidinedione (5-FU), peplomycin sulfate) as compared to HSC-2 cells. Lower concentrations of CDDP, but not other anticancer drugs, induced comparable cytostatic effects on both HSC-2 and HepG2 cells. CDDP induced internucleosomal DNA fragmentation and activation of caspases 3, 8 and 9 in HepG2 cells. On the other hand, CDDP did not induce DNA fragmentation and activated caspase 3 only marginally in HSC-2 cells. Combination treatment with CDDP (10 microM) and 5-FU (100 microM) additively activated all three caspases in HepG2 cells, but not in HSC-2 cells. The present study demonstrated the chemotherapeutic potential of combined treatment of CDDP and 5-FU against hepatoma cells and the considerable variation of drug sensitivity between cancer cell lines.