Gallium maltolate is a promising chemotherapeutic agent for the treatment of hepatocellular carcinoma.
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.


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 microM for gallium nitrate and 25-35 microM for gallium maltolate). Gallium maltolate at 30 microM 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.


CONCLUSIONS
These data support clinical testing of gallium maltolate, an orally active compound, in the treatment of HCC.
Chua
Mei-Sze
MS
Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305-5655, USA. mchua@stanford.edu
Bernstein
Lawrence R
LR
Li
Rui
R
So
Samuel K S
SK
D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005708:Gallium / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009942:Organometallic Compounds / Q000494:pharmacology*; D011753:Pyrones / Q000494:pharmacology*; D011990:Receptors, Transferrin / Q000096:biosynthesis / Q000235:genetics; D012262:Ribonucleoside Diphosphate Reductase / Q000096:biosynthesis / Q000235:genetics
D009942:Organometallic Compounds; D011753:Pyrones; D011990:Receptors, Transferrin; C512662:gallium maltolate; D005708:Gallium; C093713:ribonucleotide reductase M2; D012262:Ribonucleoside Diphosphate Reductase; C027235:gallium nitrate