Saucernetin-7 isolated from Saururus chinensis induces caspase-dependent apoptosis in human promyelocytic leukemia HL-60 cells.

Abstract

In the present study, we investigated the effect of saucernetin-7 (a biologically active compound isolated from the underground parts of Saururus chinensi) on the induction of apoptosis and the putative pathways of its action in HL-60 human promyelocytic leukemia cells. Saucernetin-7-treated HL-60 cells displayed several features of apoptosis, including DNA fragmentation, DNA laddering by agarose gel electrophoresis, and externalization of annexin-V targeted phosphatidylserine (PS) residues. z-VAD-fmk (a broad-caspase inhibitor) almost completely suppressed saucernetin-7-induced DNA ladder formation, thereby implicating the caspase cascade in the apoptotic process. We also observed that saucernetin-7 caused the activations of caspase-3, -8 and -9, and that it induced Bid cleavage, the mitochondrial translocation of Bax from the cytosol, and cytochrome c release from mitochondria, but it had no effect on Bcl-2 and Bcl-xL levels. Taken together, the present study demonstrates that saucernetin-7 is a potent inducer of apoptosis and that its activity is facilitated by caspase-8 activation, Bid cleavage, Bax translocation to mitochondria, release of cytochrome c into cytoplasm, and subsequently caspase-3 activation, which offers a potential mechanism for the apoptosis-inducing activity of saucernetin-7.

• Authors: Seung-Ki Choi, Bo-Rim Seo, Kyung-Won Lee, Woong Cho, Seoung-Hee Jeong, Kyung-Tae Lee
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 30 Issue 8 Pg. 1516-22 (Aug 2007) ISSN: 0918-6158 [Print] Japan
• PMID: 17666813 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Annexin A5
• Furans
• Lignans
• Phosphatidylserines
• Proto-Oncogene Proteins c-bcl-2
• saucernetin-7
• Cytochromes c
• Caspases

Topics

• Annexin A5 (metabolism)
• Apoptosis (drug effects)
• Blotting, Western
• Caspases (physiology)
• Cell Division (drug effects)
• Cytochromes c (metabolism)
• Cytosol (drug effects, metabolism)
• DNA Fragmentation (drug effects)
• Furans (isolation & purification, pharmacology)
• HL-60 Cells
• Humans
• Lignans (isolation & purification, pharmacology)
• Membrane Potentials (drug effects)
• Mitochondria (drug effects, metabolism)
• Mitochondrial Membranes (drug effects)
• Phosphatidylserines (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (biosynthesis, genetics)
• Saururaceae (chemistry)