Induction of Cell Cycle Arrest and Apoptosis by Ruthenium Complex cis-(Dichloro)tetramineruthenium(III) Chloride in Human Lung Carcinoma Cells A549

Abstract

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.

Anticancer Ruthenium(III) Complexes and Ru(III)-Containing Nanoformulations: An Update on the Mechanism of Action and Biological Activity

“…Therefore, the overall morphological analysis outcomes provided strong evidence of an apoptosis-inducing activity, in line with several in vitro studies supporting apoptotic events to explain the anticancer properties of different ruthenium derivatives, both in their +2 and +3 oxidation states [47,78,112,140,141,153,[155][156][157][158][159][160][161]. However, also other different molecular pathways can be involved in the cell death process [153].…”

“…Therefore, the overall morphological analysis outcomes provided strong evidence of an apoptosis-inducing activity, in line with several in vitro studies supporting apoptotic events to explain the anticancer properties of different ruthenium derivatives, both in their +2 and +3 oxidation states. [47,78,112,140,141,153,[155][156][157][158][159][160][161] However, also other different molecular pathways can be involved in the cell death process. [153] In fact, in the case of MCF-7 cells treated with the DoHuRu/DOTAP liposomes at IC50 conc., in addition to apoptotic hallmarks, also autophagic vacuoles were clearly detectable, suggesting morphological changes associated with autophagy activation (Figure 9c, inset).…”

Antitumor effectiveness and mechanism of action of Ru(II)/amino acid/diphosphine complexes in the peritoneal carcinomatosis progression

“…10 They show less toxicity, they are selective of tumor cells, and present a novel mechanism of action, the prospect of non-cross-resistance and a different spectrum of activity. [11][12][13][14][15][16][17][18][19] In a previous study, we recently reported that complexes with the general formula [Ru(AA-H)(dppb)(bipy)] PF 6 (AA-H = amino acid anion) inhibited the growth of Ehrlich carcinoma cells in vitro. 20 Among the Ru(II)/ amino acid/diphosphine complexes evaluated, those with l-methionine and l-tryptophan present the best activity against Ehrlich carcinoma cells, with IC 50 values (concentration that results in a 50% reduction in cellular viability) of 10.2 ± 2.3 µM and 8.7 ± 3.1 µM, respectively.…”

“…10 They show less toxicity, they are selective of tumor cells, and present a novel mechanism of action, the prospect of non-cross-resistance and a different spectrum of activity. 11–19…”

Cis-[RuCl(BzCN)(N–N)(P–P)]PF6 complexes: Synthesis and in vitro antitumor activity

“…The samples were incubated at 4°C in the dark and analyzed by flow cytometry (FACSCalibur, BD Biosciences, San José, CA, . The percentage of cells in phases sub-G1, G0/G1, S, and G2/M was analyzed using the ModFitLT software (Verity Software House, Topsham, ME, USA)[30].…”