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

Ching Tung Lum, Zhen Fan Yang, Hoi Yee Li, Raymond Wai Yin Sun, Sheung Tat Fan, Ronnie Tung Ping Poon, Marie C.M. Lin, Chi Ming Che, Hsiang Fu Kung

Research output: Journal article publicationJournal articleAcademic researchpeer-review

74 Citations (Scopus)

Abstract

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-la 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-la 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.

Original languageEnglish
Pages (from-to)1527-1538
Number of pages12
JournalInternational Journal of Cancer
Volume118
Issue number6
DOIs
Publication statusPublished - 15 Mar 2006
Externally publishedYes

Keywords

  • Apoptosis
  • Chemocytotoxic
  • Gold(III) compound
  • Growth arrest and dna damage (Gadd) inducible genes
  • Hepatocellular carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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