Loss of mitochondrial transmembrane potential and caspase-9 activation during apoptosis induced by the novel styryl-lactone goniothalamin in HL-60 leukemia cells.

Abstract

Styryl-lactones such as goniothalamin represent a new class of compounds with potential anti-cancer properties. In this study, we investigated the mechanisms of goniothalamin (GTN), a plant styryl-lactone induced apoptosis in human promyelocytic leukemia HL-60 cells. This plant extract resulted in apoptosis in HL-60 cells as assessed by the externalisation of phosphatidylserine. Using the mitochondrial membrane dye (DIOC(6)) in conjunction with flow cytometry, we found that GTN treated HL-60 cells demonstrated a loss of mitochondrial transmembrane potential (Deltapsi(m)). Further immunoblotting on these cells showed activation of initiator caspase-9 and the executioner caspases-3 and -7. Pretreatment with the pharmacological caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp fluoromethyl ketone (Z-VAD.FMK) abrogated apoptosis as assessed by all of the apoptotic features in this study. In summary, our results demonstrate that goniothalamin-induced apoptosis occurs via the mitochondrial pathway in a caspase dependent manner.

• Authors: S H Inayat-Hussain, B O Annuar, L B Din, A M Ali, D Ross
• Journal: Toxicology in vitro : an international journal published in association with BIBRA (Toxicol In Vitro) Vol. 17 Issue 4 Pg. 433-9 (Aug 2003) ISSN: 0887-2333 [Print] England
• PMID: 12849726 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Indicators and Reagents
• Pyrones
• goniothalamin
• CASP3 protein, human
• CASP7 protein, human
• CASP9 protein, human
• Caspase 3
• Caspase 7
• Caspase 9
• Caspases

Topics

• Apoptosis (physiology)
• Caspase 3
• Caspase 7
• Caspase 9
• Caspases (metabolism)
• Enzyme Activation (drug effects)
• Flow Cytometry
• HL-60 Cells
• Humans
• Indicators and Reagents
• Membrane Potentials (drug effects)
• Mitochondria (physiology)
• Pyrones (pharmacology)