IDENTIFICATION OF MOLECULAR TARGETS OF TRIS DBA [TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0)]

Abstract

Cancer is complex disease involving complex genetic and epigenetic heterogeneity making it the second leading cause of death globally after heart disease. While conventional treatments like surgery, radiotherapy, chemotherapy are principal strategies, the focus is shifting to therapies that can target multiple pathways to treat cancers. In the present report, it is hypothesized that Tris DBA, an organometallic compound, inhibits proliferation and tumor growth, and induces apoptosis in multiple myeloma (MM) and hepatocellular carcinoma (HCC) cells, thereby potentially exhibiting a broad spectrum of anticancer effects. The results clearly indicated that Tris DBA could substantially inhibit both constitutive and IL-6 inducible STAT3 activation and abrogate proliferation/survival of MM and HCC cells by negatively regulating STAT3 activation by (1) SHP-2 upregulation and (2) Suppression of JAK/Src activation. Additionally, the compound exhibits potent antitumor activity in vivo, with little to no acute toxicity. A phospho-proteomic profiling has revealed several key phosphorylation changes induced by Tris DBA treatment which indicate broad anticancer potential of the compound. Further work is warranted to completely understand the binding partner of Tris DBA.