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

S. H. Inayat-Hussain, B. O. Annuar, L. B. Din, A. M. Ali, D. Ross

    Research output: Contribution to journalArticle

    98 Citations (Scopus)

    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 (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.

    Original languageEnglish
    Pages (from-to)433-439
    Number of pages7
    JournalToxicology in Vitro
    Volume17
    Issue number4
    DOIs
    Publication statusPublished - Aug 2003

    Fingerprint

    Caspase 9
    HL-60 Cells
    Lactones
    Membrane Potentials
    Leukemia
    Chemical activation
    Apoptosis
    Initiator Caspases
    Caspase 7
    Caspase Inhibitors
    Flow cytometry
    Phosphatidylserines
    Plant Extracts
    Mitochondrial Membranes
    Caspases
    Ketones
    Immunoblotting
    Caspase 3
    Flow Cytometry
    Coloring Agents

    Keywords

    • Apoptosis
    • Caspase activation
    • Goniothalamin
    • Mitochondrial transmembrane potential
    • Styryl-lactone

    ASJC Scopus subject areas

    • Toxicology

    Cite this

    Loss of mitochondrial transmembrane potential and caspase-9 activation during apoptosis induced by the novel styryl-lactone goniothalamin in HL-60 leukemia cells. / Inayat-Hussain, S. H.; Annuar, B. O.; Din, L. B.; Ali, A. M.; Ross, D.

    In: Toxicology in Vitro, Vol. 17, No. 4, 08.2003, p. 433-439.

    Research output: Contribution to journalArticle

    Inayat-Hussain, S. H. ; Annuar, B. O. ; Din, L. B. ; Ali, A. M. ; Ross, D. / Loss of mitochondrial transmembrane potential and caspase-9 activation during apoptosis induced by the novel styryl-lactone goniothalamin in HL-60 leukemia cells. In: Toxicology in Vitro. 2003 ; Vol. 17, No. 4. pp. 433-439.
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