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.


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 of caspase-3 activity and a decrease of cell proliferation and 3H-thymidine incorporation. No significant change could be observed for the activity of sphingomyelinase and sphingomyelin content.


CONCLUSIONS
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
Liu
Jian-Jun
JJ
Cell Biology B, Biomedical Center, University of Lund, Sweden.
Wang
Ji-Yao
JY
Hertervig
Erik
E
Nilsson
Ake
A
Duan
Rui-Dong
RD
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D013467:Sulindac / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D013467:Sulindac; C025462:sulindac sulfide; D013108:Sphingomyelin Phosphodiesterase; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; C025463:sulindac sulfone