Activation of caspase-3 protease via a Bcl-2-insensitive pathway during the process of ginsenoside Rh2-induced apoptosis.

Abstract

We have demonstrated that ginsenoside Rh2 (G-Rh2), a ginseng saponin with a dammarane skeleton, induces apoptosis of human hepatoma SK-HEP-1 cells as evidenced by analyses of DNA fragmentation, flow cytometry and changes in cell morphology. Ac-YVAD-CMK or Ac-DEVD-CHO effectively prevented G-Rh2-induced DNA fragmentation, indicating the involvement of caspase-like proteases in the process of apoptosis. In addition, G-Rh2 induced the processing of caspase-3 to an active form, p17. In stable Bcl-2 transfectants, G-Rh2 also induced DNA fragmentation, while staurosporine-induced DNA fragmentation was totally blocked. As it did in wild-type cells, G-Rh2 induced the proteolytic activation of caspase-3 protease and subsequent cleavage of PARP in the bcl-2 transfectants. In summary, G-Rh2 contains an apoptotic inducing activity in SK-HEP-1 cells which functions via Bcl-2-insensitive activation of caspase-3, followed by proteolytic cleavage of PARP.

• Authors: J A Park, K Y Lee, Y J Oh, K W Kim, S K Lee
• Journal: Cancer letters (Cancer Lett) Vol. 121 Issue 1 Pg. 73-81 (Dec 16 1997) ISSN: 0304-3835 [Print] Ireland
• PMID: 9459177 (Publication Type: Journal Article)

Chemical References

• Drugs, Chinese Herbal
• Enzyme Precursors
• Ginsenosides
• Protease Inhibitors
• Proto-Oncogene Proteins c-bcl-2
• Saponins
• ginsenoside Rh2
• Endopeptidases
• CASP3 protein, human
• Caspase 3
• Caspases
• Cysteine Endopeptidases
• Staurosporine

Topics

• Apoptosis (drug effects)
• Blotting, Western
• Carcinoma, Hepatocellular (enzymology, pathology)
• Caspase 3
• Caspases
• Cell Size (drug effects)
• Cell Survival (drug effects)
• Cysteine Endopeptidases (metabolism)
• Dose-Response Relationship, Drug
• Drugs, Chinese Herbal (pharmacology)
• Endopeptidases (biosynthesis)
• Enzyme Activation
• Enzyme Precursors (metabolism)
• Flow Cytometry
• Ginsenosides
• Humans
• Panax (physiology)
• Plants, Medicinal
• Protease Inhibitors (pharmacology)
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
• Saponins (pharmacology)
• Staurosporine (pharmacology)
• Transfection
• Tumor Cells, Cultured