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[Cancer Research 65, 2441-2448, March 15, 2005]
© 2005 American Association for Cancer Research

Experimental Therapeutics, Molecular Targets, and Chemical Biology

Mimicry of a Cellular Low Energy Status Blocks Tumor Cell Anabolism and Suppresses the Malignant Phenotype

Johannes V. Swinnen1, Annelies Beckers1, Koen Brusselmans1, Sophie Organe1, Joanna Segers1, Leen Timmermans1, Frank Vanderhoydonc1, Ludo Deboel1, Rita Derua2, Etienne Waelkens2, Ellen De Schrijver1, Tine Van de Sande1, Agnès Noël3, Fabienne Foufelle4 and Guido Verhoeven1

1 Laboratory for Experimental Medicine and Endocrinology and 2 Division of Biochemistry, University of Leuven, Leuven, Belgium; 3 Laboratory of Tumor and Developmental Biology, University of Liege, Tour de Pathologie (B23), Sart-Tilman, Liege, Belgium; and 4 Institut National de la Santé et de la Recherche Médicale, Centre de Recherches Biomédicales des Cordeliers, Université Paris 6, Paris, France

Requests for reprints: Johannes V. Swinnen, Laboratory for Experimental Medicine and Endocrinology, University of Leuven, Gasthuisberg O&N, Herestraat 49 bus 902, B-3000 Leuven, Belgium. Phone: 32-16-345970; Fax: 32-16-345934; E-mail: johan.swinnen{at}med.kuleuven.ac.be.

Aggressive cancer cells typically show a high rate of energy-consuming anabolic processes driving the synthesis of lipids, proteins, and DNA. Here, we took advantage of the ability of the cell-permeable nucleoside 5-aminoimidazole-4-carboxamide (AICA) riboside to increase the intracellular levels of AICA ribotide, an AMP analogue, mimicking a low energy status of the cell. Treatment of cancer cells with AICA riboside impeded lipogenesis, decreased protein translation, and blocked DNA synthesis. Cells treated with AICA riboside stopped proliferating and lost their invasive properties and their ability to form colonies. When administered in vivo, AICA riboside attenuated the growth of MDA-MB-231 tumors in nude mice. These findings point toward a central tie between energy, anabolism, and cancer and suggest that the cellular energy sensing machinery in cancer cells is an exploitable target for cancer prevention and/or therapy.

Key Words: AICA • anabolism • AMPK • energy • cancer




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Cancer Research Clinical Cancer Research
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Copyright © 2005 by the American Association for Cancer Research.