Novel Isatin-based activator of p53 transcriptional functions in tumor cells.

Abstract

Bioinorganic medicinal chemistry remains a hot field for research aimed at developing novel anti-cancer treatments. Discovery of metal complexes as potent antitumor chemotherapeutics such as cisplatin led to a significant shift of focus toward organometallic/ bioinorganic compounds containing transition metals and their chelates as novel scaffolds for drug discovery. In that way, transition metal complexes coordinated to essential biological scaffolds represent a highly promising class of compounds for design of novel target-specific therapeutics. Here, we report novel data on p53 activating Isatin-based Cu(II) complex exhibiting cytotoxic properties towards HCT116 and MCF7 tumor cell lines, as confirmed by cell viability assay and flow cytometry analysis of apoptosis. Furthermore, putative p53-mediated mechanism of action of this compound is supported by quantitative analysis of <i>TP53</i>, <i>MDM2</i> and <i>PUMA</i> genes expression, as well as luciferase-based p53 pathway activation assay. Multiplex immunoassay analysis of inflammatory markers revealed potential modulation of several cytokines and chemokines.