A novel anti-tumor agent, Ln(III) 2-thioacetate benzothiazole induces anti-angiogenic effect and cell death in cancer cell lines

New complexes with a potent DNA-binding anti-tumor agent, europium(III)- and terbium(III)-2-thioacetate benzothiazole were synthesized and characterized. These complexes showed strong binding affinity to calf thymus DNA using fluorometric and electronic absorption spectroscopy. The synthesized complexes resulted in inhibition of proliferation of EAC cells and ascites formation. Their anti-tumor effect was found to be through anti-angiogenic activity as was evident by the reduction of microvessel density and down-regulation of VEGF receptor type-2 (Flk-1). It was found that EAC cells had distinct DNA fragmentation patterns analyzed by capillary electrophoresis in the treated animals. Moreover, the synthesized complexes exhibited significant cytotoxic activity against HepG2 and MCF7 cell lines. Furthermore, complexes showed a potent anti-bacterial activity against two pathogenic bacteria Escherichia coli and Salmonella.

Graphical AbstractNew complexes with a potent DNA-binding anti-tumor agent, Europium(III) and Terbium(III)-2-thioacetate benzothiazole were synthesized, new complexes showed promising anti-tumor activity and anti-bacterial activity.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► New Ln(III)-2-thioacetate benzothiazole complexes were synthesized and characterized. ► Complexes showed promising antitumor activity with IC50 less than 5 μM against MCF7. ► In vivo, complexes down-regulate the expression of VEGF and CD31 in EAC cancer cell. ► The new complexes displayed remarkable in vitro and in vivo anticancer activity. ► Ln(III)-complexes displayed a pronounced activity against the two pathogenic bacteria.