title: In vitro and in vivo biological characterization of the anti-proliferative potential of a cyclic trinuclear organotin(iv) complex.
abstract: Identification of novel molecules that can selectively inhibit the growth of tumor cells, avoid causing side effects to patients and/or intrinsic or acquired resistance, usually associated with common chemotherapeutic agents, is of utmost importance. Organometallic compounds have gained importance in oncologic chemotherapy, such as organotin(iv) complexes. In this study, we assessed the anti-tumor activity of the cyclic trinuclear organotin(iv) complex with an aromatic oximehydroxamic acid group [nBu2Sn(L)]3(H2L = N,2-dihydroxy-5-[N-hydroxyethanimidoyl]benzamide) - MG85 - and provided further characterization of its biological targets. We have previously shown the high anti-proliferative activity of this complex against human colorectal and hepatocellular carcinoma cell lines and lower cytotoxicity in neonatal non-tumor fibroblasts. MG85 induces tumor cell apoptosis and down-regulation of proteins related to tubulin dynamics (TCTP and COF1). Further characterization included the: (i) evaluation of interference in the cell cycle progression, including the expression of critical genes; (ii) affinity to DNA and the corresponding mode of binding; (iii) genotoxic potential in cells with deficient DNA repair pathways; and (iv) in vivo tumor reduction efficiency using mouse colorectal carcinoma xenografts.
authors: School of Public Health, Physiotherapy and Sports Science, UCD Centre for Food Safety, Centre for Molecular Innovation and Drug Discovery, University College Dublin, Belfield, Dublin 4, Ireland.
authors: Marta
authors: M
authors: Martins
authors: UCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologias, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal. ma.fernandes@fct.unl.pt.
authors: Pedro V
authors: PV
authors: Baptista
authors: UCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologias, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal. ma.fernandes@fct.unl.pt.
authors: Ana Soraia
authors: AS
authors: Mendo
authors: UCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologias, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal. ma.fernandes@fct.unl.pt.
authors: Claudia
authors: C
authors: Correia
authors: UCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologias, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal. ma.fernandes@fct.unl.pt and CEDOC, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal.
authors: Paula
authors: P
authors: Videira
authors: Centre for Toxicogenomics and Human Health, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal.
authors: António S
authors: AS
authors: Rodrigues
authors: UCIBIO-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Caparica 2829-516, Portugal.
authors: J
authors: J
authors: Muthukumaran
authors: UCIBIO-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Caparica 2829-516, Portugal.
authors: Teresa
authors: T
authors: Santos-Silva
authors: UCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologias, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal. ma.fernandes@fct.unl.pt.
authors: Ana
authors: A
authors: Silva
authors: Centro de Química Estrutural, Complexo I, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal.
authors: M Fátima C Guedes
authors: MF
authors: da Silva
authors: Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, Lisboa, Portugal.
authors: Joana
authors: J
authors: Gigante
authors: Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, Lisboa, Portugal.
authors: António
authors: A
authors: Duarte
authors: Centro de Química Estrutural, Complexo I, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal.
authors: Malgorzata
authors: M
authors: Gajewska
authors: UCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologias, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal. ma.fernandes@fct.unl.pt and Centro de Química Estrutural, Complexo I, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal.
authors: Alexandra R
authors: AR
authors: Fernandes
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002417:Cattle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002869:Chromosome Aberrations; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism; D005434:Flow Cytometry; D008297:Male; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000378:metabolism; D009947:Organotin Compounds / Q000493:pharmacokinetics*; D058105:Polymerization; D013056:Spectrophotometry, Ultraviolet; D014404:Tubulin / Q000378:metabolism; D000090324:Tumor Protein, Translationally-Controlled 1
chemical_list: D009363:Neoplasm Proteins; D009947:Organotin Compounds; C000715647:TPT1 protein, human; C000715648:Tpt1 protein, mouse; D014404:Tubulin; D000090324:Tumor Protein, Translationally-Controlled 1; D004247:DNA; C427203:calf thymus DNA; D053148:Caspase 3; D053179:Caspase 7