Unexplored features of Ru(ii) polypyridyl complexes – towards combined cytotoxic and antimetastatic activity

Abstract

The well-documented cytotoxic activity of coordinatively saturated and substitutionally inert polypyridyl Ru(II) complexes substantiates their high potency as antiproliferative agents against primary tumors. However, the primary cause of cancer morbidity and mortality responsible for about 90% of cancer deaths is the occurrence of metastasis. Therefore, scientists have to concentrate their efforts on designing compounds affecting not only the primary tumor, but also efficiently inhibiting metastasis. Herein, we report two families of Ru(II) polypyridyl complexes bearing 2,2′-bipyridine substituted by a semicarbazone 2-formylopyridine moiety as one of the ligands and 4,4′-di-tert-butyl-2,2′-dipyridyl or 4,7-diphenyl-1,10-phenanthroline as auxiliary ligands. These complexes strengthen cells’ adherent properties and inhibit the activity of metalloproteinases (MMPs) in vitro, which is relevant in anti-metastatic treatment. The in vitro studies were performed on human lung adenocarcinoma (A549) and human pancreatic cancer (PANC-1) cells, which have a well-documented invasive potential. The induced alteration of the tumor cells’ adhesion properties correlated with the high cytotoxic effect exerted by the complexes and their excellent cellular uptake. It was also proved that both complexes directly inhibit M-MP2 and M-MP9 enzyme activities, which are essential for the development of tumor metastasis. The results of this study indicate that the biological properties of polypyridyl Ru(II) complexes extend beyond the standard cytotoxic activity and represent an important step towards designing new anti-metastatic agents.