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.
|Journal||Journal of Inorganic Biochemistry|
|State||Published - Jan 2022|
Bibliographical noteFunding Information:
This work was supported by the Goiás State Research Foundation (FAPEG) [grant number 2012/12 ]; São Paulo Research Foundation (FAPESP) [grant number 2014/10516-7 ]; Coordination for the Improvement of Higher Education Personnel (CAPES) [grant number 2014/1267732 ]; and Brazilian National Council for Scientific and Technological Development (CNPq) [grant number 207516/2014-6 ].
- Cell death
- Cytotoxicity activity
ASJC Scopus subject areas
- Inorganic Chemistry