Xia Z, Lundgren B, Bergstrand A, DePierre J W, Nässberger L
Unit for Biochemical Toxicology, Department of Biochemistry, Stockholm University, S-106 91, Stockholm, Sweden.
Biochem Pharmacol. 1999 May 15;57(10):1199-208. doi: 10.1016/s0006-2952(99)00009-x.
In order to investigate the molecular mechanism of the antineoplastic effects exerted by the antidepressive agents imipramine, clomipramine, and citalopram, we examined the effects of these compounds on cell viability, generation of reactive oxygen species (ROS), and mitochondrial membrane potential (DeltaPsi(m)) in human acute myeloid leukemia HL-60 cells. Our results indicate that exposure to these compounds causes a loss in cell viability by activating the apoptotic process, as identified by electron microscopy, DNA gel electrophoresis, and flow cytometry. The increased generation of ROS induced by these drugs was a relatively early event and preceded the loss of DeltaPsi(m). Overexpression of the antiapoptotic protein Bcl-2 or Bcl-X(L) prevents antidepressant-induced apoptosis, as well as loss of DeltaPsi(m), but does not affect the generation of ROS.
为了研究抗抑郁药丙咪嗪、氯米帕明和西酞普兰发挥抗肿瘤作用的分子机制，我们检测了这些化合物对人急性髓性白血病HL-60细胞的细胞活力、活性氧（ROS）生成以及线粒体膜电位（ΔΨm）的影响。我们的结果表明，通过电子显微镜、DNA凝胶电泳和流式细胞术鉴定，暴露于这些化合物会通过激活凋亡过程导致细胞活力丧失。这些药物诱导的ROS生成增加是一个相对早期的事件，且发生在ΔΨm丧失之前。抗凋亡蛋白Bcl-2或Bcl-X(L)的过表达可预防抗抑郁药诱导的凋亡以及ΔΨm的丧失，但不影响ROS的生成。
