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 6 mg kg-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.