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

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 a...

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Bibliographic Details
Main Authors: Inayat Hussain, Salmaan Hussain, Osman, Md. Anuar, Din, Laily, Ali, Abdul Manaf, Ross, David
Format: Article
Language:English
English
Published: Elsevier 2003
Online Access:http://psasir.upm.edu.my/id/eprint/40315/1/Loss%20of%20mitochondrial%20transmembrane%20potential%20and%20caspase-9%20activation%20during%20apoptosis%20induced%20by%20the%20novel%20styryl-lactone%20goniothalamin%20in%20HL-60%20leukemia%20cells.pdf
http://psasir.upm.edu.my/id/eprint/40315/7/1-s2.0-S0887233303000511-main.pdf
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Summary: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 (DIOC6) in conjunction with flow cytometry, we found that GTN treated HL-60 cells demonstrated a loss of mitochondrial transmembrane potential (Δψm). 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.