Glaucocalyxin A induces apoptosis in human leukemia HL-60 cells through mitochondria-mediated death pathway.

Abstract

Glaucocalyxin A (GLA) is a biologically active ent-kauranoid diterpenoid isolated from Rabdosia japonica var. glaucocalyx, a traditional Chinese medicinal herb, which has been shown to inhibit tumor cell proliferation. However, the mechanism underlying GLA-induced cytotoxicity remains unclear. In this study, we focused on the effect of GLA induction on apoptosis, the mitochondria-mediated death pathway and the accumulation of reactive oxygen species (ROS) in human leukemia cells (HL-60). GLA could induce a dose-dependent apoptosis in HL-60 cells as characterized by cell morphology, DNA fragmentation, activation of caspase-3, -9 and an increased expression ratio of Bax/Bcl-2. The mitochondrial membrane potential (Δψ(m)) loss and cytochrome c release from mitochondria to cytosol were observed during the induction. Moreover, GLA caused a time- and dose-dependent elevation of intracellular ROS level in HL-60 cells, and N-acetyl-l-cysteine (NAC, a well-known antioxidant) could block GLA-induced ROS generation and apoptosis. These data suggest that GLA induces apoptosis in HL-60 cells through ROS-dependent mitochondrial dysfunction pathway.

• Authors: Li Wen Gao, Jian Zhang, Wen Hua Yang, Bin Wang, Jian Wen Wang
• Journal: Toxicology in vitro : an international journal published in association with BIBRA (Toxicol In Vitro) Vol. 25 Issue 1 Pg. 51-63 (Feb 2011) ISSN: 1879-3177 [Electronic] England
• PMID: 20851175 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Antioxidants
• Biomarkers
• Diterpenes, Kaurane
• Drugs, Chinese Herbal
• Reactive Oxygen Species
• glaucocalyxin A
• CASP3 protein, human
• CASP9 protein, human
• Caspase 3
• Caspase 9

Topics

• Antineoplastic Agents, Phytogenic (antagonists & inhibitors, pharmacology)
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Biomarkers (metabolism)
• Caspase 3 (metabolism)
• Caspase 9 (metabolism)
• Cell Line, Tumor
• Cell Survival (drug effects)
• DNA Fragmentation (drug effects)
• Diterpenes, Kaurane (antagonists & inhibitors, pharmacology)
• Drugs, Chinese Herbal (pharmacology)
• G1 Phase (drug effects)
• HL-60 Cells
• Humans
• Inhibitory Concentration 50
• Leukemia (drug therapy, metabolism, pathology)
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondria (drug effects, enzymology, metabolism)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)