Anti-Proliferative Potential of a Co(II) Coordination Compound Bearing 1,10-Phenanthroline-5,6-Dione: DNA and Protein Interaction Studies and Its Application in Cancer Therapy

摘要

It is of utmost importance to persistently evaluate the antitumor properties of novel compounds when seeking for alternatives that may overcome major drawbacks of commonly used chemotherapeutic agents. We recently described a novel agent - [Co (Cl)(H[2]O)(DION)[2]][BF[4]] (DION = 1,10-phenanthroline-5,6-dione - showing very high anti-proliferative activity of) against three human tumor cell lines (IC[50] < 1 uM), being selective towards colorectal tumor cell line. Here, we focus on the mechanisms of action underlying this promising anti-tumor potential. As we previously reported, this complex induces cell cycle arrest in S-phase and subsequent cell death by apoptosis, whilst reducing the expression of proteins typically up-regulated in tumors. In the present work we demonstrate that (i) the Co(II) phendione complex does not reduce the viability of non-tumorigenic breast epithelial cells by > 85% at 1 uM; (ii) but up-regulates pro-apoptotic Bax and cell cycle-related p21; and (iii) induces release of lactate dehydrogenase, which is partially reverted by ursodeoxycholic acid.