Apoptosis induction of human leukemia U937 cells by gomisin N, a dibenzocyclooctadiene lignan, isolated from Schizandra chinensis Baill.

Abstract

We compared the pro-apoptotic effect of two dibenzocyclooctadiene lignans, gomisin A and gomisin N, isolated from Schizandra chinensis Baill, in U937 human promyelocytic leukemia cells in vitro. Gomisin N, but not gomisin A, inhibited cell growth in a dose-dependent manner, which was associated with the induction of apoptosis. The increase in apoptosis that was induced by gomisin N was correlated with down-regulation of anti-apoptotic Bcl-2 expression, a decrease in the mitochondrial membrane potential (MMP) and a release of cytochrome c from the mitochondria into the cytosol. Furthermore, gomisin N induced the proteolytic activation of caspase-9 and -3 and a concomitant degradation of poly(ADP-ribose) polymerase. However, caspase-8 was not activated and cleavage of Bid was not observed in gomisin N-treated U937 cells. The cytotoxic effects and apoptotic characteristics induced by gomisin N were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, demonstrating the important role that caspase-3 plays in the process. We conclude that gomisin N induces the apoptosis of U937 cells through a signaling cascade of mitochondria-mediated intrinsic caspase pathways and gomisin N may be a useful chemotherapeutic agent.

• Authors: Jong-Hwan Kim, Young-Whan Choi, Cheol Park, Cheng-Yun Jin, You Jin Lee, Da Jung Park, Sun Guen Kim, Gi-Young Kim, Il-Whan Choi, Won-Deuk Hwang, Yong Kee Jeong, Se-Kwon Kim, Yung Hyun Choi
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 48 Issue 3 Pg. 807-13 (Mar 2010) ISSN: 1873-6351 [Electronic] England
• PMID: 20034537 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Caspase Inhibitors
• Cyclooctanes
• Dioxoles
• Lignans
• Polycyclic Compounds
• schizandrin B
• Cyclin D1
• schizandrol B
• Cytochromes c
• Caspase 3

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• Caspase 3 (metabolism)
• Caspase Inhibitors
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cyclin D1 (metabolism)
• Cyclooctanes (pharmacology)
• Cytochromes c (metabolism)
• DNA Fragmentation
• Dioxoles (pharmacology)
• Flow Cytometry
• Fruit (chemistry)
• G1 Phase (drug effects)
• Humans
• Lignans (pharmacology)
• Mitochondria (drug effects, metabolism)
• Polycyclic Compounds (pharmacology)
• Schisandra (chemistry)
• U937 Cells