Graduate School of Life Science and Biotechnology, Pochon CHA University, CHA Stem Cell Institute, Seoul, Korea.
Pharmacology. 2009;84(5):300-9. doi: 10.1159/000245937. Epub 2009 Oct 14.
Doxorubicin (DOX) is involved in the induction of DNA damage, inhibition of cell proliferation, impairment of mitochondria, and cell death. To determine the biological effects of DOX in murine lymphocytes, we analyzed cell proliferation, cell cycle status, and apoptosis in Ba/F3 and EL4 lymphoid cells. DOX treatment resulted in significant cellular morphological alteration with increased intracellular granularity and cell size. DOX inhibited cell proliferation through cell cycle arrest at the G(2)/M phase as well as by cell death. In addition, DOX treatment dramatically upregulated Fas expression and enhanced caspase activation to promote intracellular apoptotic signaling for cell death. Treatment with an agonistic antibody stimulated Fas and accelerated the cell death effects. In conclusion, we demonstrate that DOX induces cell cycle arrest and apoptosis by increased Fas expression and ultimately results in enhanced cell death.
多柔比星（DOX）参与诱导 DNA 损伤、抑制细胞增殖、损害线粒体和细胞死亡。为了确定 DOX 在鼠淋巴细胞中的生物学效应，我们分析了 Ba/F3 和 EL4 淋巴样细胞的细胞增殖、细胞周期状态和细胞凋亡。DOX 处理导致细胞形态发生显著变化，细胞内颗粒增多，细胞体积增大。DOX 通过细胞周期阻滞在 G2/M 期以及细胞死亡抑制细胞增殖。此外，DOX 处理显著上调 Fas 表达并增强半胱天冬酶激活，以促进细胞内凋亡信号转导导致细胞死亡。用激动性抗体处理刺激 Fas 并加速细胞死亡作用。总之，我们证明 DOX 通过增加 Fas 表达诱导细胞周期阻滞和凋亡，最终导致增强的细胞死亡。
