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

Marta Martins, PV Baptista, Ana Soraia Mendo, C Correia, Paula Videira, AS Rodrigues, Jayaraman Muthukumaran, Teresa Santos-Silva, Ana Silva, M. Fatima C. Guedes da Silva, Joana Gigante, Antonio Duarte, Malgorzata Gajewska, AR Fernandes

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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 [nBu(2)Sn(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.

Original languageEnglish
Pages (from-to)1015-1023
Number of pages9
JournalMolecular Biosystems
Volume12
Issue number3
DOIs
Publication statusPublished - 2016

Keywords

  • CELL-CYCLE
  • ANTITUMOR-ACTIVITY
  • DNA-DAMAGE
  • INDUCED ENDOREDUPLICATION
  • PROTEIN-INTERACTION
  • METAL-COMPLEXES
  • P21
  • BINDING
  • AGENTS
  • DERIVATIVES

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