Author(s)

Il Han Song, Suk Bae Kim, Hyun Duk Shin, Ha Yan Kang, Eun Young Kim

Division of Hepatology and Gastroenterology, Department of Internal Medicine, Dankook University College of Medicine, Dankook University Hospital Institute of Medical Science, Cheonan , Korea.

The present study was conducted to investigate whether mitochondrial pathway of apoptosis is involved in cyclooxygenase-2 (COX-2) inhibitor-induced growth inhibition of hepatoma cells. The growth rate and pattern of NS-398 (selective COX-2 inhibitor)-treated Hep3B hepatoma cells were analyzed by microscopic examination, DNA fragmentation gel analysis and flow cytometry followed by the cleavage of down-stream caspase 3 and the release of cytosolic fraction of cytochrome c assessed by Western blot analysis. NS-398 induced the growth inhibition of hepatoma cells depending on the concentration of this COX-2 inhibitor and time sequence. Ladder patterned-DNA fragmentation and cytometric redistribution to sub-G1 phase in cell cycle were revealed in NS-398-induced growth inhibition of hepatoma cells. Cytochrome c was translocated from mitochondria to cytosol in time-dependent manner following NS-398 treatment to hepatoma cells. COX-2 inhibitor induces the growth inhibition of hepatoma cells via caspase-dependent, mitochondria-mediated intrinsic apoptosis pathway. These results strongly suggest the possibility of therapeutic implication of COX-2 inhibitor in HCC.

Hepatocellular Carcinoma; Cyclooxygenase-2 (COX-2); COX-2 Inhibitor; Apoptosis; Western Blotting; Flow Cytometry; DNA

Song, I. , Kim, S. , Shin, H. , Kang, H. and Kim, E. (2012) NS-398 induces caspase-dependent, mitochondria-mediated intrinsic apoptosis of hepatoma cells. Advances in Bioscience and Biotechnology, 3, 649-656. doi: 10.4236/abb.2012.326084.