INDUCTION OF APOPTOSIS IN HEPG2 HUMAN HEPATOCELLULAR-CARCINOMA CELLS BY A NOVEL DERIVATIVE OF URSODEOXYCHOLIC ACID (UDCA)

The effects of ursodeoxycholic acid (UDCA) and its novel derivative, n amed as HS-1030, on the proliferation of HepG2, human hepatocellular c arcinoma cells were investigated. Whereas UDCA had no significant effe ct in a concentration range we have tested, HS-1030 inhibited the prol iferation of HepG2 cells in a concentration dependent manner. Surprisi ngly, HS-1030 had no effect on the proliferation of Human Chang liver cell which is a normal liver cell line. We also found that proliferati on-inhibitory effect of HS-1030 was due to the induction of apoptosis of HepG2 cells, which was confirmed by observing the internucleosomal DNA fragmentation and morphological changes (i.e., cell shrinkage, nuc lear condensation and the formation of apoptotic bodies). These result s suggest that HS-1030 may be a good candidate as a drug for the treat ment of liver cancer.