Synthetic chenodeoxycholic acid derivative, HS-1200, induces apoptosis of human hepatoma cells via a mitochondrial pathway.

Abstract

We investigated whether HS-1200 has anti-proliferation effects on human hepatoma cells in vitro. Here, chromatin condensation, DNA ladder formation and proteolytic cleavage of poly (ADP-ribose) polymerase (PARP) were observed after treatment of HS-1200, indicating the occurrence of apoptotic cell death, which was associated with up-regulation of Bax, cleaved-caspase-3 and cleaved-caspase-9. Inhibition of caspase-9 rescued HS-1200-induced apoptosis. Furthermore, cells treated with HS-1200 showed a reduction in mitochondrial membrane potential (Deltapsi(m)) and caused cytochrome c release into the cytosol. The results indicated that synthetic chenodeoxycholic acid HS-1200 could induce cell apoptosis in BEL7402 human hepatoma cell line, via a Bax/cytochrome c/caspase-9 independent pathway. This study suggested that HS-1200 is potentially useful as an apoptosis inducer for the treatment of hepatocellular carcinoma.

• Authors: Hui Liu, Cheng-Kun Qin, Guo-Qing Han, Hong-Wei Xu, Wan-Hua Ren, Cheng-Yong Qin
• Journal: Cancer letters (Cancer Lett) Vol. 270 Issue 2 Pg. 242-9 (Nov 08 2008) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 18565645 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• BAX protein, human
• Caspase Inhibitors
• Cysteine Proteinase Inhibitors
• HS 1200
• Proto-Oncogene Proteins c-bcl-2
• bcl-2-Associated X Protein
• Chenodeoxycholic Acid
• Cytochromes c
• Poly(ADP-ribose) Polymerases
• CASP8 protein, human
• CASP9 protein, human
• Caspase 8
• Caspase 9

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Carcinoma, Hepatocellular (enzymology, pathology)
• Caspase 8 (metabolism)
• Caspase 9 (metabolism)
• Caspase Inhibitors
• Cell Proliferation (drug effects)
• Chenodeoxycholic Acid (analogs & derivatives, pharmacology)
• Cysteine Proteinase Inhibitors (pharmacology)
• Cytochromes c (metabolism)
• Dose-Response Relationship, Drug
• Flow Cytometry
• Humans
• Liver Neoplasms (enzymology, pathology)
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondria (drug effects, enzymology, pathology)
• Poly(ADP-ribose) Polymerases (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• bcl-2-Associated X Protein (metabolism)