In vitro cytotoxicity, cellular uptake, reactive oxygen species and cell cycle arrest studies of novel ruthenium(II) polypyridyl complexes towards A549 lung cancer cell line

Abstract

Ruthenium(II) polypyridyl complexes have displayed some promising biological responses against a variety of cancers and have emerged as a potential candidate that can show significant antitumor activity. Three ruthenium(II) polypyridyl complexes were biologically evaluated in vitro against the A549 cancer cell line. The complexes were selected based on initial DNA intercalation studies and MTT viability screening and were selected based on the most promising candidates, the [Ru(bpy)₂o-CPIP].2PF6 (complex 1), [Ru(phen)₂o-CPIP].2PF6 (complex 2) and [Ru(biq)₂o-CPIP].2PF6 (complex 3). Confocal cellular uptake studies confirmed the intracellular transport of complexes into A549. Cytoplasmic and the nucleic accumulation of the complex 1 and 2 was seen while no fluorescent microscopy was performed for complex 3 due to instrumental limitations. Cellular cytotoxicity was investigated with the aid of the Alamar blue assay. The complexes displayed concentration and time dependent inhibitory effects yielding IC₅₀ values from 5.00 to 32.75 µM. Complex 1 exhibit highest cytotoxicity with IC₅₀ value of 5.00 ± 1.24 µM. All of the complexes have shown a significant effect in the reduction of intracellular reactive oxygen species (ROS) levels. Finally, the complexes have shown a transient effect on the cell cycle by arresting it at G0/G1 phase except for complex 2 [Ru(phen)₂o-CPIP].2PF6 which has shown the significant G0/G1 arrest.

Keywords:

• Ruthenium(II) polypyridyl complexes
• A549
• cytotoxic activity
• cellular uptake
• reactive oxygen species
• G0/G1 arrest

Acknowledgements

The authors acknowledged the support provided through the funding program ‘‘Fiosraigh Scholarship 2016’’ to conduct this research work.

Disclosure statement

There is no conflict of interest declared by the authors.