Gallium Maltolate is a Promising Chemotherapeutic Agent for the Treatment of Hepatocellular Carcinoma

Abstract

Background: Hepatocellular carcinoma (HCC) is a particularly lethal cancer with few treatment options. Since gallium is known to accumulate specifically in HCC tumors but not in non-tumor liver, we investigated two gallium compounds, gallium nitrate (GaN) and gallium maltolate (GaM), as potential new agents for treating HCC. Materials and Methods: The anti-proliferative and apoptotic activities of GaN and GaM were assessed in vitro using four HCC cell lines. HCC gene expression data was analyzed to provide a mechanistic rationale for using gallium in the treatment of HCC. Results: Both compounds showed dose-dependent antiproliferative activity in all four HCC cell lines after 6-day drug exposure (IC₅₀ values range from 60-250 μM for gallium nitrate and 25-35 μM for gallium maltolate). Gallium maltolate at 30 μM additionally induced apoptosis after 6 days. HCC gene expression data showed significantly elevated expression of the M2 subunit of ribonucleotide reductase, which is a target for the antiproliferative activity of gallium. Conclusion: These data support clinical testing of gallium maltolate, an orally active compound, in the treatment of HCC.