Ru(II)/amino acid complexes inhibit the progression of breast cancer cells through multiple mechanism-induced apoptosis

Francyelli Mello-Andrade, Adriana P.M. Guedes, Wanessa C. Pires, Vivianne S. Velozo-Sá, Kezia A. Delmond, Davi Mendes, Matheus S. Molina, Larissa Matuda, Maria Alice Montes de Sousa, Paulo Melo-Reis, Clever C. Gomes, Carlos Henrique Castro, Márcio Aurélio P. Almeida, Carlos F.M. Menck, Alzir A. Batista, Ravshan Burikhanov, Vivek M. Rangnekar, Elisângela Silveira-Lacerda

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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.

Original languageEnglish
Article number111625
JournalJournal of Inorganic Biochemistry
Volume226
DOIs
StatePublished - Jan 2022

Bibliographical note

Funding 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 ].

Publisher Copyright:
© 2021

Keywords

  • Cell death
  • Cytotoxicity activity
  • Genotoxicity
  • Par-4
  • Ruthenium

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry

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