Cancer Lett 2011 Dec;313 (2): 201-10. [IF:4.864]
Involvement of reactive oxygen species in 2-methoxyestradiol-induced apoptosis in human neuroblastoma cells.
Zhang Q , Ma Y , Cheng YF , Li WJ , Zhang Z , Chen SY .
School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, China.
郑州大学药学院
Abstract
Neuroblastoma is the most common extra-cranial solid tumor in children. Despite advances in the treatment of childhood cancer, outcomes for children with advanced-stage neuroblastoma remain poor. Here we reported that 2-methoxyestradiol (2-ME) inhibited the proliferation and induced apoptosis in human neuroblastoma SK-N-SH and SH-SY5Y cells. 2-ME treatment also resulted in the generation of ROS and the loss of mitochondrial membrane potential in SK-N-SH and SH-SY5Y, indicating that 2-ME-induced apoptosis is mediated by ROS. This is supported by the results that have shown that co-treatment with antioxidants, VC, L-GSH and MitoQ(10), decreased 2-ME-induced generation of ROS and the loss of the mitochondrial membrane potential, increased the Bcl-2/Bax ratio, decreased 2-ME-induced activation of caspase-9 and caspase-3 and the up-regulation of apoptosis-inducing factor (AIF), and prevented 2-ME-induced apoptosis in SK-N-SH and SH-SY5Y cells. These results suggested that oxidative stress plays an important role in 2-ME-induced apoptotic death of human neuroblastoma cells.
摘要：
神经母细胞瘤是儿童中最常见的颅外实体瘤。尽管在儿童肿瘤的治疗上有很大的进展，但对处于进展期神经母细胞瘤的治疗仍然很缺乏。在这里，我们提出2-甲氧雌二醇能抑制人类神经母细胞瘤SK-N-SH和SH-SY5Y细胞的增殖并能诱导其凋亡。在SK-N-SH和SH-SY5Y细胞中，2-甲氧雌二醇可能是通过活性氧的产生和使线粒体膜丢失发挥作用的，这表明2-甲氧雌二醇诱导细胞凋亡是通过活性氧介导的。这个结果已经得到证实。当2-甲氧雌二醇与抗氧化剂，维他命c，L-谷胱甘肽和MitoQ同时使用时，会使2-甲氧雌二醇诱导产生的活性氧和线粒体膜丢失的可能性降低，使Bcl-2/Bax比值上升，降低caspase-9和caspase-3的激活，降低凋亡诱导因子上调，并且预防2-甲氧雌二醇诱导SK-N-SH和SH-SY5Y细胞凋亡。这些结果提示氧化应激在2-甲氧雌二醇诱导人类神经母细胞瘤细胞凋亡中起重要作用。
