Identification of molecular targets of Tris DBA [Tris(dibenzylideneacetone)dipalladium(0)] for cancer therapy

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, we hypothesized that Tris DBA, an organometallic compound, can inhibit proliferation, tumor growth, and induce apoptosis in multiple myeloma (MM) and hepatocellular carcinoma (HCC) cells, thereby potentially exhibiting significant anticancer effects. Our preliminary results clearly indicated that Tris DBA could substantially inhibit both constitutive as well as IL-6 inducible STAT3 activation and abrogate proliferation/survival in MM and HCC cells. A phospho-proteomic profiling revealed several key phosphorylation changes induced by Tris DBA treatment which further indicate broad anticancer potential of the compound. Additionally, the agent exhibited potent antitumor actvitiy in vivo, with little adverse effects. The ongoing work is aimed at investigating the possible binding target(s) of Tris DBA and further characterize the molecular mechanism(s) underlying STAT3 inhibitory effects of the drug. Citation Format: Loukik Arora, Chris Soon Heng Tan, Radoslaw M. Sobota, Gautam Sethi. Identification of molecular targets of Tris DBA [Tris(dibenzylideneacetone)dipalladium(0)] for cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1240.