Saucernetin-7 isolated from Saururus chinensis induces caspase-dependent apoptosis in human promyelocytic leukemia HL-60 cells.
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.
Choi
Seung-Ki
SK
Department of Pharmacology, College of Medicine, Pochon Cha University, Kyonggi-Do 463-712, Republic of Korea.
Seo
Bo-Rim
BR
Lee
Kyung-Won
KW
Cho
Woong
W
Jeong
Seoung-Hee
SH
Lee
Kyung-Tae
KT
D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D005663:Furans / Q000302:isolation & purification / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D017705:Lignans / Q000302:isolation & purification / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000187:drug effects; D010718:Phosphatidylserines / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D032134:Saururaceae / Q000737:chemistry*
D017304:Annexin A5; D005663:Furans; D017705:Lignans; D010718:Phosphatidylserines; D019253:Proto-Oncogene Proteins c-bcl-2; C481154:saucernetin-7; D045304:Cytochromes c; D020169:Caspases