Instituto de Ciências Biológicas-ICB I- Sala 200- UFG, Campus Samambaia (Campus II), Universidade Federal de Goiás-UFG, Goiânia, Goiás, Brazil.
Biol Trace Elem Res. 2012 Jun;147(1-3):8-15. doi: 10.1007/s12011-011-9275-7. Epub 2011 Dec 6.
Lung cancer is one of the leading causes of death in the world, and non-small cell lung carcinoma (NSCLC) accounts for approximately 75-85% of all lung cancers. In the present work, we studied the cytotoxic activity, cell cycle arrest and induction apoptosis of the compound cis-(dichloro)tetramineruthenium(III) chloride {cis-[RuCl(2)(NH(3))(4)]Cl} in human lung carcinoma tumor cell line A549. The results of MTT and trypan blue assays showed that cis-[RuCl(2)(NH(3))(4)]Cl causes reduction in the viability of A549 cells when treating with 95 and 383 μM of the compound for 48 and 72 h. Lower concentrations of the compound (19, 3.8 and 0.38 μM), however, only slightly affected cell viability. The IC(50) value for the compound was about 383 μM. Survival analysis of the A549 cells after treatment with ruthenium(III) compound using long term clonogenic assay showed that it reduced colony formation ability at concentrations of 0.38 and 3.8 μM, and at concentrations of 95 and 383 μM no colonies were observed. Cell cycle analysis showed that compound ruthenium led to an accumulation of A549 cells in S phase and increased in the sub-G1 peak. In addition, cis-(dichloro)tetramineruthenium(III) chloride treatment induced apoptosis, as observed by the increased numbers of annexin V-positive cells and increased messenger RNA expression of caspase-3.
肺癌是世界上主要的死亡原因之一，非小细胞肺癌（NSCLC）约占所有肺癌的 75-85%。在本工作中，我们研究了化合物顺式-（二氯）四氨合钌（III）氯化物{顺式-[RuCl（2）（NH（3））（4）]Cl}对人肺癌肿瘤细胞系 A549 的细胞毒性、细胞周期停滞和诱导凋亡作用。MTT 和台盼蓝检测结果表明，当用 95 和 383 μM 的化合物处理 A549 细胞 48 和 72 h 时，顺式-[RuCl（2）（NH（3））（4）]Cl 导致细胞活力降低。然而，较低浓度的化合物（19、3.8 和 0.38 μM）仅略微影响细胞活力。该化合物的 IC（50）值约为 383 μM。用长期集落形成实验对 A549 细胞用钌（III）化合物处理后的存活分析表明，在 0.38 和 3.8 μM 的浓度下降低了集落形成能力，而在 95 和 383 μM 的浓度下没有观察到集落。细胞周期分析表明，化合物钌导致 A549 细胞在 S 期积累，并增加了 sub-G1 峰。此外，顺式-（二氯）四氨合钌（III）氯化物处理诱导了细胞凋亡，通过增加 annexin V 阳性细胞的数量和 caspase-3 信使 RNA 表达观察到。
