Abstract
Ruthenium complexes have been extensively explored as potential molecules for cancer treatment. Considering our previous findings on the remarkable cytotoxic activity exhibited by the ruthenium (II) complex 3-hydroxy-4-methoxybenzoate (hmxbato)-cis-[RuII(ŋ2-O2CC7H7O2)(dppm)2]PF6 against Leishmania promastigotes and also the similar metabolic characteristics between trypanosomatids and tumor cells, the present study aimed to analyze the anticancer potential of hmxbato against lung tumor cells, as well as the partial death mechanisms involved. Hmxbato demonstrated selective cytotoxicity against A549 lung tumor cells. In addition, this complex at a concentration of 3.8 µM was able to expressively increase the generation of reactive oxygen species (ROS) in tumor cells, causing an oxidative stress that may culminate in: (1) reduction in cellular proliferation; (2) changes in cell morphology and organization patterns of the actin cytoskeleton; (3) cell arrest in the G2/M phase of the cell cycle; (4) apoptosis; (5) changes in the mitochondrial membrane potential and (6) initial DNA damage. Furthermore, we demonstrated that the induction of programmed cell death can occur by the intrinsic apoptotic pathway through the activation of caspases. It is also worth highlighting that hmxbato exhibited predominant actions on A549 tumor cells in comparison to BEAS-2B normal bronchial epithelium cells, which makes this complex an interesting candidate for the design of new drugs against lung cancer.
Highlights
Ruthenium complexes have been extensively explored as potential molecules for cancer treatment
The results show that the metal–ligand association resulted in an effective complex against A549 lung tumor cells
Some studies of our research group have investigated the cytotoxic potential of different ruthenium complexes against parasites of the Leishmania genus[10,30] (Costa et al, 2017; Miranda et al, 2018), and we have demonstrated the probable cell death mechanism triggered by ruthenium complex called 3-hydroxy-4-methoxybenzoate-cis-[RuII(ŋ2-O2CC7H7O2)(dppm)2]PF6 against Leishmania (Leishmania) amazonensis promastigotes[11]
Summary
Ruthenium complexes have been extensively explored as potential molecules for cancer treatment. Numerous disadvantages are associated with the use of cisplatin and its derivatives as antitumor agents, namely: (1) drug resistance, which can be developed after treatment; (2) low toxicity against some types of cancer, such as cervical, lung and pancreatic cancer; and (3) low selectivity for tumor cells, triggering several side effects. These disadvantages have encouraged the development of new metal complex-based chemotherapeutic agents that have higher and more selective toxicities on tumor c ells[3,4]. Ruthenium is interesting due to its low toxicity, good stability and ability to mimic iron by binding to plasma proteins such as albumin and ferritin[3,5,6]
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