Cytotoxic (salen)ruthenium(iii) anticancer complexes exhibit different modes of cell death directed by axial ligands

Abstract

A cancer-cell selective bis(guanidine)-ruthenium(iii) complex induces apoptosis, whereas its amidine analogue effectively kills cancer cells through paraptosis pathways.

Anticancer Ruthenium(III) Complexes and Ru(III)-Containing Nanoformulations: An Update on the Mechanism of Action and Biological Activity

“…Overall, these data highlighted the crucial role played by the cellular uptake process in determining the anticancer efficacy of Ru(III)-based drugs, showing both POPC and DOTAP-based liposomes as very efficient nanocarriers for the stabilization of Ru complexes in aqueous media and their effective transport in cells. Particularly relevant was their clear detection in the nucleus, differently from other known Ru(III)complexes, able to accumulate in the cytoplasm but not in the nuclear region [153]. Notably, for these systems cationic DOTAP nanoaggregates proved to be more effective as Ru(III)-based drugs carriers, showing faster uptake kinetics [77,79,100,106].…”

“…Particularly relevant was their clear detection in the nucleus, differently from other known Ru(III)complexes, able to accumulate in the cytoplasm but not in the nuclear region. [153] Notably, for these systems cationic DOTAP nanoaggregates proved to be more effective as Ru(III)-based drugs carriers, showing faster uptake kinetics. [77,79,100,106] Overall, analysis of the dansyl-dependent fluorescence emission over time indicated that the HoThyDansRu/DOTAP nanoaggregates first localized within the cell membranes, then entered the cytoplasm, spreading to the whole cell, including perinuclear and nuclear compartments (Figure 8b) [100].…”

“…Therefore, the overall morphological analysis outcomes provided strong evidence of an apoptosis-inducing activity, in line with several in vitro studies supporting apoptotic events to explain the anticancer properties of different ruthenium derivatives, both in their +2 and +3 oxidation states. [47,78,112,140,141,153,[155][156][157][158][159][160][161] However, also other different molecular pathways can be involved in the cell death process. [153] In fact, in the case of MCF-7 cells treated with the DoHuRu/DOTAP liposomes at IC50 conc., in addition to apoptotic hallmarks, also autophagic vacuoles were clearly detectable, suggesting morphological changes associated with autophagy activation (Figure 9c, inset).…”

“…[47,78,112,140,141,153,[155][156][157][158][159][160][161] However, also other different molecular pathways can be involved in the cell death process. [153] In fact, in the case of MCF-7 cells treated with the DoHuRu/DOTAP liposomes at IC50 conc., in addition to apoptotic hallmarks, also autophagic vacuoles were clearly detectable, suggesting morphological changes associated with autophagy activation (Figure 9c, inset). [134] In the case of cytomorphological modifications induced by the treatment with the aminoacyl lipid Ru(III) compound I hosted in DOTAP liposomes, not only malignant cells such as MCF-7, HeLa and C6 but also normal cell lines as 3T3-L1 (mouse embryo fibroblast) and HaCaT (human keratinocytes) were analysed by phase-contrast light microscopy in the absence and presence of the drug.…”

Tamoxifen - DEBIO 1143 kombinasyonunun östrojen reseptörü pozitif meme kanseri hücre hatlarındaki etkisi.

“…Bursch et al [23] showed that inhibition of autophagy inhibited TAM-induced cell death in MCF-7 cells. In another study, autophagosome formation in MCF-7 cells exposed to TAM was imaged through dansylcadaverine, a fluorescent probe of autophagosome [28]. Hwang et al [29] found that autophagy was induced independent of ER as light chain-3-II (LC3-II) increased in ER+ MCF-7 and ER-SKBR-3 breast cancer cells which were exposed to TAM [26].…”