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 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.
Inayat-Hussain
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Department of Biomedical Science, Faculty of Allied Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz 50300, Kuala Lumpur, Malaysia. michalia@tm.net.my
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D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D053179:Caspase 7; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D007202:Indicators and Reagents; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000502:physiology*; D011753:Pyrones / Q000494:pharmacology*
D007202:Indicators and Reagents; D011753:Pyrones; C103280:goniothalamin; C505407:CASP3 protein, human; C505520:CASP7 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053179:Caspase 7; D053453:Caspase 9; D020169:Caspases