Journal
CANCER
Volume 115, Issue 19, Pages 4459-4469Publisher
WILEY
DOI: 10.1002/cncr.24514
Keywords
gold (III); complexes; apoptosis; cell cycle arrest; colon cancer
Categories
Funding
- Areas of Excellence Scheme [AoE/ P-10/01]
- Gastroenterological Research Fund of University of Hong Kong, Hong Kong, China
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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 (111) complex la (gold 1a) exhibited strong cytotoxicity in some tumor cell lines. In the current study, the effect of gold la was investigated on colon cancer cells. METHODS: The cytotoxicity of gold la 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 la 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 mu M to 3.4 mu M, which represented 8.7-fold to 20.8-fold greater potency than that of cisplatin. Gold la 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, p2l, p27 and Bax. In vivo, intraperitoneal injection of gold la 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 la at effective antitumor concentrations did not cause any toxic side effects in mice. CONCLUSIONS: The current results suggested that gold la may be a new potential therapeutic drug for colon cancer. Cancer 2009;115:4459-69. (C) 2009 American Cancer Society.
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