title: Antiproliferative effects of ruthenium-based nucleolipidic nanoaggregates in human models of breast cancer in vitro: insights into their mode of action.
abstract: Looking for new metal-based anticancer treatments, in recent years many ruthenium complexes have been proposed as effective and safe potential drugs. In this context we have recently developed a novel approach for the in vivo delivery of Ru(III) complexes, preparing stable ruthenium-based nucleolipidic nanoaggregates endowed with significant antiproliferative activity. Herein we describe the cellular response to our ruthenium-containing formulations in selected models of human breast cancer. By in vitro bioscreens in the context of preclinical studies, we have focused on their ability to inhibit breast cancer cell proliferation by the activation of the intrinsic apoptotic pathway, possibly via mitochondrial perturbations involving Bcl-2 family members and predisposing to programmed cell death. In addition, the most efficient ruthenium-containing cationic nanoaggregates we have hitherto developed are able to elicit both extrinsic and intrinsic apoptosis, as well as autophagy. To limit chemoresistance and counteract uncontrolled proliferation, multiple cell death pathways activation by metal-based chemotherapeutics is a challenging, yet very promising strategy for targeted therapy development in aggressive cancer diseases, such as triple-negative breast cancer with limited treatment options. These outcomes provide valuable, original knowledge on ruthenium-based candidate drugs and new insights for future optimized cancer treatment protocols.
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", Via D. Montesano 49, 80131-Naples, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Irace
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, University of Campania "Luigi Vanvitelli", Via L. De Crecchio 7, 80138-Naples, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Misso
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", Via D. Montesano 49, 80131-Naples, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Capuozzo
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", Via D. Montesano 49, 80131-Naples, Italy.
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Piccolo
authors.affiliation: Department of Chemical Sciences, University of Naples "Federico II", Via Cintia 21, 80126-Naples, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Riccardi
authors.affiliation: Department of Chemical Sciences, University of Naples "Federico II", Via Cintia 21, 80126-Naples, Italy.|Institut Laue-Langevin, 71 Avenue des Martyrs, 38000, Grenoble, France.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Luchini
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, University of Campania "Luigi Vanvitelli", Via L. De Crecchio 7, 80138-Naples, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Caraglia
authors.affiliation: Department of Chemical Sciences, University of Naples "Federico II", Via Cintia 21, 80126-Naples, Italy.|CSGI - Consorzio Sistemi a Grande Interfase, Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019-Sesto Fiorentino (FI) Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Paduano
authors.affiliation: Department of Chemical Sciences, University of Naples "Federico II", Via Cintia 21, 80126-Naples, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Montesarchio
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", Via D. Montesano 49, 80131-Naples, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Santamaria
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D061986:MCF-7 Cells; D053761:Nanocomposites / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D012428:Ruthenium / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D012428:Ruthenium