2-Aminoethoxydiphenyl borate (2-APB) is a widely used agent in the studies of IP3 receptor and store-operated channel signaling (Bootman et al., 2002; Flemming et al., 2003). We previously demonstrated that 2-APB significantly inhibits the HEK-293 cell growth and the mechanism is not related to the IP3 receptors (Xu et al., 2005). Recently, we also found TRPC1 and TRPC5, are involved in the vascular smooth muscle cell proliferation and migration (Xu et al., 2006) and neointimal growth (Kumar et al., 2006). However the effect of 2-APB and the involvement of TRP channels on the cancer cell growth and death are not clear. In this study we used cell proliferation and apoptosis assay kits to examine the effects of 2-APB on the cancer cells including human breast adenocarcinoma cell line MCF-7, human lung carcinoma cells A549, human ovarian cancer cells SKOV-3 and human hepatocellular liver carcinoma cell line HepG2. The cells were grown in DMEM-F12 (Gibco, UK) medium containing 10% fetal calf serum, 100 units/ml penicillin and 100 µg/ml streptomycin, and were maintained at 37°C under 95% air and 5% CO2. Cells were seeded onto 96-well cell culture plates for experiments. The unpaired student’s t test was used to assess the statistical difference. The cell proliferation of SKOV-3 cells and HEK-293 cells were significantly inhibited by 2-APB in a concentration dependent manner after 24 h treatment. The minimum effective concentration occurred at 0.5 μM and the EC50 was 5.9 μM. However, the effect of 2-APB on the proliferation of MCF-7 and A549 cells was not concentration-dependent. 2-APB at 10, 50 μM displayed as an antiproliferative effect on MCF-7 cells, but no effect was observed at a higher concentration (100 μM). Moreover, the lung and liver cancer cells (A549 and HepG2) were resistant to 2-APB. The antiproliferative effect were not related to the gap junctional blocking effect of 2-APB, since carbenoxolone, a gap junction blocker, did not change the effect of 2-APB. In addition, 2-APB also significantly evoked the apoptosis of the cancer cells detected by anti-histone-complexed DNA fragmentation assay. The data indicate 2-APB inhibits cancer cell growth by its anti-proliferative and pro-apoptotic mechanisms. 2-APB sensitive TRP channels or store-operated channels may be the potential drug targets for anticancer therapy. The differential sensitivity to 2-APB suggests 2-APB or its analogues could be developed as specific agents for some types of cancer.