Gold (III) porphyrin complexes induce apoptosis and cell cycle arrest and inhibit tumor growth in colon cancer |
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| Authors: | Shuiping Tu MD PhD Raymond Wai‐Yin Sun PhD Marie C M Lin PhD Jian Tao Cui MD Bing Zou MD PhD Qing Gu PhD Hsiang‐Fu Kung PhD Chi‐Ming Che PhD Benjamin C Y Wong MD PhD |
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| Institution: | 1. Department of Medicine, the University of Hong Kong, Hong Kong, China;2. Department of Chemistry and Open Laboratory of Chemical Biology of the Institute of Molecular Technology for Drug Discovery and Synthesis, the University of Hong Kong, Hong Kong, China;3. Li Ka Shing Institute of Health Sciences and Center for Emerging Infectious Diseases, the Chinese University of Hong Kong, Hong Kong, China;4. Fax: (011) 852‐29049443 |
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| Abstract: | BACKGROUND: Gold (III) compounds have exhibited favorable antitumor properties both in vitro and in vivo. In a previous study, the authors reported that the novel gold (III) complex 1a (gold 1a) exhibited strong cytotoxicity in some tumor cell lines. In the current study, the effect of gold 1a was investigated on colon cancer cells. METHODS: The cytotoxicity of gold 1a was determined by using the 3‐(4,5‐dimethyl‐2‐thihazyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide method. Flow cytometry was used to detect apoptosis and cell cycle. The expression of protein was evaluated by Western blot assay. Tumor growth in vivo was evaluated in nude mice. RESULTS: Gold 1a exhibited marked cytotoxic effects in vitro to human colon cancer, and the concentration of drug required to inhibit cell growth by 50% compared with control (IC50) values ranged from 0.2 μM to 3.4 μM, which represented 8.7‐fold to 20.8‐fold greater potency than that of cisplatin. Gold 1a significantly induced apoptosis and cell cycle arrest and cleaved caspase 3, caspase 7, and poly(ADP‐ribose) polymerase; released cytochrome C, and up‐regulated p53, p21, p27, and Bax. In vivo, intraperitoneal injection of gold 1a at doses of 1.5 mg/kg and 3.0 mg/kg significantly inhibited tumor cell proliferation, induced apoptosis, and suppressed colon cancer tumor growth. An acute toxicology study indicated that gold 1a at effective antitumor concentrations did not cause any toxic side effects in mice. CONCLUSIONS: The current results suggested that gold 1a may be a new potential therapeutic drug for colon cancer. Cancer 2009. © 2009 American Cancer Society. |
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| Keywords: | gold (III) complexes apoptosis cell cycle arrest colon cancer |
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