Z-ajoene induces apoptosis of HL-60 cells: involvement of Bcl-2 cleavage.
Garlic organosulfur components exhibit antitumor activity, but the molecular mechanisms underlying these effects have not been well characterized. We showed that Z-ajoene, a sulfur-rich compound purified from garlic, induced time- and dose-dependent apoptosis in HL-60 cells. This process implied the activation of caspase-3 and the cleavage of the antiapoptotic protein Bcl-2. The caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-[OMe]-fluoromethylketone inhibited Bcl-2 cleavage and apoptosis induced by Z-ajoene. This effect was partially prevented by treatment of HL-60 cells with the antioxidant N-acetylcysteine. Hence, the transmission of apoptotic signal induced by Z-ajoene involved a reactive oxygen species-dependent pathway leading to caspase-dependent Bcl-2 cleavage.
Li
Min
M
National Research Laboratories of Natural and Biomimetic Drugs, Peking University, Beijing, China.
Min
Ji-Mei
JM
Cui
Jing-Rong
JR
Zhang
Li-He
LH
Wang
Kui
K
Valette
Annie
A
Davrinche
Christian
C
Wright
Michel
M
Leung-Tack
Jeanne
J
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D004220:Disulfides / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D013454:Sulfoxides
D000970:Antineoplastic Agents; D004220:Disulfides; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D013454:Sulfoxides; C048980:ajoene; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases