Li Min, Min Ji-Mei, Cui Jing-Rong, Zhang Li-He, Wang Kui, Valette Annie, Davrinche Christian, Wright Michel, Leung-Tack Jeanne
National Research Laboratories of Natural and Biomimetic Drugs, Peking University, Beijing, China.
Nutr Cancer. 2002;42(2):241-7. doi: 10.1207/S15327914NC422_14.
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.
大蒜有机硫成分具有抗肿瘤活性，但其作用的分子机制尚未完全明确。我们发现，从大蒜中提纯的富含硫的化合物Z-ajoene可诱导HL-60细胞发生时间和剂量依赖性凋亡。这一过程意味着半胱天冬酶-3的激活以及抗凋亡蛋白Bcl-2的裂解。半胱天冬酶抑制剂苄氧羰基-Val-Ala-Asp-[OMe]-氟甲基酮可抑制Z-ajoene诱导的Bcl-2裂解和凋亡。抗氧化剂N-乙酰半胱氨酸处理HL-60细胞可部分阻止这种效应。因此，Z-ajoene诱导的凋亡信号传递涉及一条依赖活性氧的途径，导致半胱天冬酶依赖性的Bcl-2裂解。
