
Ru(II)/amino acid complexes inhibit the progression of breast cancer cells through multiple mechanism-induced apoptosis
2021; Elsevier BV; Volume: 226; Linguagem: Inglês
10.1016/j.jinorgbio.2021.111625
ISSN1873-3344
AutoresFrancyelli Mello-Andrade, Adriana P. M. Guedes, Wanessa Carvalho Pires, Vivianne S. Velozo-Sá, Kézia Aguiar Delmond, Davi Mendes, Matheus S. Molina, Larissa Matuda Macedo, Maria Alice Montes de Sousa, Paulo Roberto de Melo Reis, Cléver Gomes Cardoso, Carlos H. Castro, M. Almeida, Carlos Frederico Martins Menck, Alzir A. Batista, Ravshan Burikhanov, Vivek M. Rangnekar, Elisângela de Paula Silveira-Lacerda,
Tópico(s)Advanced biosensing and bioanalysis techniques
ResumoFor 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.
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