Cytotoxic effect, antitumour activity and toxicity of organotin derivatives with ortho- or para-hydroxy-benzoic acids

• DOI: 10.1007/s00044-018-2135-7
• Publication Date: 2018-02-02T13:23:13Z
• Authors: Maria S. Agiorgiti; Angelos Evangelou; Patra Vezyraki; Sotiris K. Hadjik...; Vasiliki Kalfakakou; Ioannis Tsanaktsidis; Anna Batistatou; John Zelovitis; Yannis V. Simos; Vasilios Ragos; Spyridon Karkabounas; Dimitrios Peschos
• Keywords: Benzoic acid

The cytotoxic and antitumour activities of five organotin complexes (1–5) with o-hydroxy-benzoic or p-hydroxy-benzoic acids were evaluated in a series of in vitro and in vivo experiments. All complexes exhibited strong cytotoxic activity against all cancer cells lines, whereas complexes 1, 2 and 4 induced apoptosis at significantly lower doses than complexes 3 and 5. Human cancer cells treated with increasing concentrations of complexes 1, 2 and 4 gradually lost their ability to form colonies. Only complexes 1 and 2 inhibited colony formation efficiency in rat leiomyosarcoma cells. Histopathology of liver and kidney showed mild damage and lung oedema after a single injection of 10 mg/kg body wt of complex 1 to Wistar rats. At higher doses (100 mg/kg body wt) brain stem oedema was observed. Daily administration of tumour-bearing Wistar rats (leiomyosarcoma) with 1 mg/kg body wt of complex 1 until death reduced the mean tumour growth rate by more than 3× fold and prolonged mean survival time by 120%. These findings indicate that the organotin complexes with ortho- or para-hydroxy-benzoic acids possess potent cytotoxic and antitumour activity and they could be used as potential chemotherapeutic agents.