The photo-induced CO-releasing properties of the dark-stable complex [RuCl2(CO)2L] (L = 2-(pyridin-2-yl)quinoxaline) were investigated under 468 nm light exposure in the presence Show more
The photo-induced CO-releasing properties of the dark-stable complex [RuCl2(CO)2L] (L = 2-(pyridin-2-yl)quinoxaline) were investigated under 468 nm light exposure in the presence and absence of biomolecules such as histidine, calf thymus DNA and hen egg white lysozyme. The CO release kinetics were consistent regardless of the presence of these biomolecules, suggesting that they did not influence the CO release mechanism. The quinoxaline ligand demonstrated exceptional cytotoxicity against human acute monocytic leukemia cells (THP-1), with evidence of potential DNA damage ascertained by comet assay, while it remained non-toxic to normal kidney epithelial cells derived from African green monkey (Vero) cell lines. In contrast, upon light activation, the Ru(II) complex showed no toxicity against THP-1 cells but was detrimental to Vero cells. In human colorectal carcinoma (HCT-116) cells, the ligand and the Ru(II) complex produced ROS under light and dark conditions. However, HCT-116 cells retained their ability to consume oxygen and produce ATP following CO treatment, suggesting that the ROS levels were insufficient to cause significant cellular damage. Morphological features of apoptosis, including apoptotic bodies, chromatin condensation, cell shrinkage, and membrane leakage, were observed in the presence of both the ligand and its complex, irrespective of light exposure. Show less
For some cancer subtypes, such as triple-negative breast cancer, there are no specific therapies, which leads to a poor prognosis associated with invasion and metastases. Ruthenium complexes have been Show more
For some cancer subtypes, such as triple-negative breast cancer, there are no specific therapies, which leads to a poor prognosis associated with invasion and metastases. Ruthenium complexes have been developed to act in all steps of tumor growth and its progression. In this study, we investigated the effects of Ruthenium (II) complexes coupled to the amino acids methionine (RuMet) and tryptophan (RuTrp) on the induction of cell death, clonogenic survival ability, inhibition of angiogenesis, and migration of MDA-MB-231 cells (human triple-negative breast cancer). The study also demonstrated that the RuMet and RuTrp complexes induce cell cycle blockage and apoptosis of MDA-MB-231 cells, as evidenced by an increase in the number of Annexin V-positive cells, p53 phosphorylation, caspase 3 activation, and poly(ADP-ribose) polymerase cleavage. Moreover, morphological changes and loss of mitochondrial membrane potential were detected. The RuMet and RuTrp complexes induced DNA damage probably due to reactive oxygen species production related to mitochondrial membrane depolarization. Therefore, the RuMet and RuTrp complexes acted directly on breast tumor cells, leading to cell death and inhibiting their metastatic potential; this reveals the potential therapeutic action of these drugs. Show less