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has been cited by the following article:

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

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

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

  JOURNAL NAME: Advances in Bioscience and Biotechnology, Vol.3 No.6A, October 29, 2012

  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.