Sa Duck-Jin, Lee Eun-Jee, Yoo Byung-Sun
Present Address: Department of Life Science, Kyonggi University, Suwon, 443-760 Korea.
Toxicol Res. 2009 Sep;25(3):113-118. doi: 10.5487/TR.2009.25.3.113. Epub 2009 Sep 1.
Cell death induced by menadione (vitamin K-3,2-methyl-1,4-naphthoquinone) has been investigated in human promyelocytic leukemia HL-60 cells. Menadione was found to induce both apoptosis and necrosis in HL-60 cells. Low concentration (1~50 µM) of menadione induced apoptotic cell death, which was demonstrated by typical DNA ladder patterns on agarose gel electrophoresis and flow cytometry analysis. In contrast, a high concentration of menadione (100 µM) induced necrotic cell death, which was demonstrated by DNA smear pattern in agarose gel electrophoresis. Necrotic cell death was accompanied with a great reduction of cell viability. Menadione activated caspase-3, as evidenced by both increased protease activity and proteolytic cleavage of 116 kDa poly(ADP-ribose) polymerase (PARP) into 85 kDa cleavage product. Caspase-3 activity was maximum at 50 µM of menadione, and very low at 100 µM of menadione. Taken together, our results showed that menadi-one induced mixed types of cell death, apoptosis at low concentrations and necrosis at high concentrations in HL-60 cells.
已在人早幼粒细胞白血病HL - 60细胞中研究了甲萘醌（维生素K - 3，2 - 甲基 - 1，4 - 萘醌）诱导的细胞死亡。发现甲萘醌可诱导HL - 60细胞发生凋亡和坏死。低浓度（1~50 μM）的甲萘醌诱导凋亡性细胞死亡，这通过琼脂糖凝胶电泳上典型的DNA梯状条带模式和流式细胞术分析得以证实。相比之下，高浓度的甲萘醌（100 μM）诱导坏死性细胞死亡，这通过琼脂糖凝胶电泳中的DNA涂片模式得以证实。坏死性细胞死亡伴随着细胞活力的大幅降低。甲萘醌激活了半胱天冬酶 - 3，这可通过蛋白酶活性增加以及116 kDa聚（ADP - 核糖）聚合酶（PARP）被蛋白水解切割成85 kDa切割产物来证明。半胱天冬酶 - 3活性在甲萘醌浓度为50 μM时最高，而在甲萘醌浓度为100 μM时非常低。综上所述，我们的结果表明甲萘醌在HL - 60细胞中诱导了混合类型的细胞死亡，低浓度时诱导凋亡，高浓度时诱导坏死。
