NS-398 induces caspase-dependent, mitochondria-mediated intrinsic apoptosis of hepatoma cells

Abstract

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.

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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.

Conflicts of Interest

The authors declare no conflicts of interest.

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