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Mol Biosyst. 2016 Mar;12(3):1015-23. doi: 10.1039/c5mb00791g.

In vitro and in vivo biological characterization of the anti-proliferative potential of a cyclic trinuclear organotin(iv) complex.

Author information

1
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.
2
UCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologias, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal. ma.fernandes@fct.unl.pt.
3
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.
4
Centre for Toxicogenomics and Human Health, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal.
5
UCIBIO-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Caparica 2829-516, Portugal.
6
Centro de Química Estrutural, Complexo I, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal.
7
Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, Lisboa, Portugal.
8
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.

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.

PMID:
26842219
DOI:
10.1039/c5mb00791g
[Indexed for MEDLINE]

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