Metal-free imidazolium salts inhibit the growth of hepatocellular carcinoma in a mouse model.

Imidazolium salts (IMSs) are precursors to N-heterocyclic carbenes (NHCs), which are routinely used as ligands or organo-catalysts in synthetic chemistry. We recently identified several IMSs as anti-fibrotic agents in liver fibrosis, which often has a consequence in the oncogenesis of hepatocellular carcinoma (HCC). Here, we investigate the potential anti-tumor property of three IMSs (named IBN-1, IBN-9, and DPIM) in HCC cell lines and in a xenograft mouse model. Our results showed that both IBN-1 and IBN-9 significantly inhibited the cell proliferation and arrested HCC cells in the G1-phase, whereas DPIM did not have any anti-tumor activity. When tested in a Huh7 HCC xenograft mouse model, IBN-1 reduced the tumor volume by 31% (P<0.05), however accompanied by a 9% loss in body weight (P<0.005), suggesting a general toxicity. In contrast, IBN-9 significantly reduced the tumor volume by 45% (P<0.05) and 60% (P<0.01) at doses of 0.6 and 1.5 g/l in drinking water, respectively, without any loss in body weight. Our in vitro and in vivo data suggested that IBN-1 and IBN-9 inhibited the growth of HCC by suppressing the expression of Survivin and Cyclin-dependent kinases. The current study provides a proof of concept for using the metal-free IMSs to develop novel anti-cancer agents.