RGD Reference Report - Gold(III) compound is a novel chemocytotoxic agent for hepatocellular carcinoma. - Rat Genome Database

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Gold(III) compound is a novel chemocytotoxic agent for hepatocellular carcinoma.

Authors: Lum, CT  Yang, ZF  Li, HY  Wai-Yin Sun, R  Fan, ST  Poon, RT  Lin, MC  Che, CM  Kung, HF 
Citation: Lum CT, etal., Int J Cancer. 2006 Mar 15;118(6):1527-38.
RGD ID: 9999403
Pubmed: PMID:16206274   (View Abstract at PubMed)
DOI: DOI:10.1002/ijc.21484   (Journal Full-text)

Recently, a series of gold(III) meso-tetraarylporphyrins that are stable against demetallation in physiological conditions have been synthesized. In the present study, the antitumor effects of one of these compounds, gold(III) meso-tetraarylporphyrin 1a (gold-1a) was investigated in an orthotopic rat hepatocellular carcinoma (HCC) model as well as using a HCC cell line. The rat HCC model was induced by injection of rat hepatoma cells, McA-RH7777, into the left lobe of the liver. Seven days after tumor cell inoculation, gold-1a was injected directly into the tumor nodule at different doses, followed by the same doses via intraperitoneal injection twice a week. Gold-1a administration significantly prolonged the survival of HCC-bearing rats. Importantly, gold-1a induced necrosis as well as apoptosis in the tumor tissues, but not in the normal liver tissues. Furthermore, gold-1a treatment neither caused significant drop in body weight of the rats nor affected plasma aspartate aminotransferase level. In the in vitro studies, we observed that gold-1a treatment inhibited the proliferation of McA-RH7777 cells. Gold-1a upregulated genes that increase apoptosis, stabilize p53, decrease proliferation and downregulated genes playing roles in angiogenesis, invasion, and metabolism, as demonstrated by microarray. In particular, the compound upregulated 2 members of the growth arrest and DNA damage (Gadd) inducible gene family, Gadd34 and Gadd153. Suppression of Gadd34 and Gadd153 in McA-RH7777 cells by small hairpin RNA reduced the gold-1a-induced apoptosis and growth inhibition, indicating that gold-1a mediated its effects via upregulation of Gadd34 and Gadd153. Results from our study demonstrated that gold-1a might be a novel promising chemocytotoxic agent for treating HCC.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to gold(3+)  IEP 9999403 RGD 
positive regulation of apoptotic process  IMP 9999403 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ppp1r15a  (protein phosphatase 1, regulatory subunit 15A)

Additional Information