Sulindac induces apoptosis, inhibits proliferation and activates caspase-3 in Hep G2 cells

Background: It has recently been reported that sulindac has an apoptotic effect on KYN-2 cells, an undifferentiated hepatoma cell line. The present work investigates whether sulindac also has an apoptotic effect on well-differentiated hepatoma cells and what its potential mechanism might be. Materials and Methods: Hep G2 cells were treated with sulindac at different concentrations. Apoptosis rate, cell proliferation and 3H-thymidine incorporation were measured. The activities of caspase-3, acid and neutral sphingomyelinase and the changes of sphingomyelin content were also assayed. Results: Sulindac dose-dependently induced apoptosis in Hep G2 cells; both sulindac sulfone and sulfide had similar effects. The apoptosis was accompanied by an increase 3 of caspase-3 activity and a decrease of cell proliferation and H-3-thymidine incorporation. No significant change could be observed for the activity of sphingomyelinase and sphingomyelin content. Conclusion: Sulindac induces apoptosis and inhibits proliferation in Hep G2 cells. The effect may, be mediated by, a pathway related to caspase-3 activation but independent of sphingomyelin metabolism