Antitumor effectiveness and mechanism of action of Ru(II)/amino acid/diphosphine complexes in the peritoneal carcinomatosis progression
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Data
2017
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Resumo
Peritoneal carcinomatosis is considered as a potentially lethal clinical condition, and the therapeutic options are limited.
The antitumor effectiveness of the [Ru(l-Met)(bipy)(dppb)]PF6 (1) and the [Ru(l-Trp)(bipy)(dppb)]PF6 (2) complexes
were evaluated in the peritoneal carcinomatosis model, Ehrlich ascites carcinoma–bearing Swiss mice. This is the first
study that evaluated the effect of Ru(II)/amino acid complexes for antitumor activity in vivo. Complexes 1 and 2 (2 and
6mgkg−1) showed tumor growth inhibition ranging from moderate to high. The mean survival time of animal groups
treated with complexes 1 and 2 was higher than in the negative and vehicle control groups. The induction of Ehrlich ascites
carcinoma in mice led to alterations in hematological and biochemical parameters, and not the treatment with complexes
1 and 2. The treatment of Ehrlich ascites carcinoma–bearing mice with complexes 1 and 2 increased the number of
Annexin V positive cells and cleaved caspase-3 levels and induced changes in the cell morphology and in the cell cycle
phases by induction of sub-G1 and G0/G1 cell cycle arrest. In addition, these complexes reduce angiogenesis induced by
Ehrlich ascites carcinoma cells in chick embryo chorioallantoic membrane model. The treatment with the LAT1 inhibitor
decreased the sensitivity of the Ehrlich ascites carcinoma cells to complexes 1 and 2 in vitro—which suggests that the
LAT1 could be related to the mechanism of action of amino acid/ruthenium(II) complexes, consequently decreasing the
glucose uptake. Therefore, these complexes could be used to reduce tumor growth and increase mean survival time with
less toxicity than cisplatin. Besides, these complexes induce apoptosis by combination of different mechanism of action.
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Ruthenium, Peritoneal carcinomatosis, Antitumor activity, Angiogenesis, LAT1, Apoptosis
Citação
MELLO-ANDRADE, Francyelli et al. Antitumor effectiveness and mechanism of action of Ru(II)/amino acid/diphosphine complexes in the peritoneal carcinomatosis progression. Tumor Biology, Tokyo, v. 39, n. 10, e101042831769593, 2017. DOI: 10.1177/1010428317695933. Disponível em: https://journals.sagepub.com/doi/full/10.1177/1010428317695933?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org. Acesso em: 10 abr. 2025.