Altholactone, a novel styryl-lactone induces apoptosis via oxidative stress in human HL-60 leukemia cells.
Plant styryl-lactone derivatives isolated from Goniothalamus sp. are potential compounds for cancer chemotherapy. In this study, we have examined the mechanisms of apoptosis induced by altholactone, a stryl-lactone isolated from the Malaysian plant G. malayanus on human HL-60 promyelocytic leukemia cells. Flow cytometric analysis of the externalization of phosphatidylserine (PS) using the annexin V/PI method on altholactone treated HL-60 cells showed a concentration-dependent increase of apoptosis from concentrations ranging from 10.8 (2.5 microg/ml) to 172.4 microM (40 microg/ml). Pre-treatment with the antioxidant N-acetylcysteine (1 mM) completely abrogated apoptosis induced by altholactone, suggesting for the involvement of oxidative stress. Further flow cytometric assessment of the level of intracellular peroxides using the fluorescent probe 2',7'-dichlorofluorescein diacetate (DCFH-DA) confirmed that altholactone induced an increase in cellular oxidative stress in HL-60 cells which was suppressed by N-acetylcysteine. In summary, our results demonstrate for the first time that altholactone induced apoptosis in HL-60 cells occurs via oxidative stress.
Inayat-Hussain
Salmaan H
SH
Department of Biomedical Science, Faculty of Allied Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia. salmaan@medic.ukm.my
Osman
Annuar Bin
AB
Din
Laily Bin
LB
Taniguchi
Naoyuki
N
D000111:Acetylcysteine / Q000494:pharmacology; D017304:Annexin A5; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D005434:Flow Cytometry; D005452:Fluoresceins; D005663:Furans / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D007202:Indicators and Reagents; D018384:Oxidative Stress / Q000187:drug effects*; D011753:Pyrones / Q000494:pharmacology
D017304:Annexin A5; D000975:Antioxidants; D005452:Fluoresceins; D005663:Furans; D007202:Indicators and Reagents; D011753:Pyrones; C459359:altholactone; C029569:diacetyldichlorofluorescein; D000111:Acetylcysteine