NS398 inhibits the growth of Hep3B human hepatocellular carcinoma cells via caspase-independent apoptosis.
Overexpression of cyclooxygenase 2 (COX-2) is associated with the development of a number of human cancers including hepatocellular carcinoma (HCC). In addition, NS398, a selective COX-2 inhibitor, has been found to inhibit the growth of COX-2 expressing HCC cell lines. However, the mechanism of this effect remains unclear. Here, we report that NS398 inhibits the growth of the Hep 3B human HCC cell line and that inhibition results from the induction of apoptosis with no evidence of cell cycle arrest. We also show that the extent of apoptosis is greatly influenced by culture conditions. The NS398-induced apoptosis in Hep 3B cells is caspase-independent. Our data point to the feasibility of preventing HCC by means of COX-2 inhibitors, and show that the environment influences the cytotoxic effect of NS398 on cancer cells.
Park
Mi Kyung
MK
Department of Immunology, School of Medicine, Kyungpook National University, Daegu 700-422, Korea.
Hwang
Sun Young
SY
Kim
Jin Oh
JO
Kwack
Mi Hee
MH
Kim
Jung-Chul
JC
Kim
Moon Kyu
MK
Sung
Young Kwan
YK
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002470:Cell Survival; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D007211:Indoles / Q000494:pharmacology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D009578:Nitrobenzenes / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016895:Culture Media, Serum-Free; D005456:Fluorescent Dyes; D007211:Indoles; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; C007293:DAPI; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases