Portal de Periódicos da CAPES

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

2005; American Association for Cancer Research; Volume: 65; Issue: 6 Linguagem: Inglês

10.1158/0008-5472.can-04-3025

1538-7445

Johannes V. Swinnen, Annelies Beckers, Koen Brusselmans, Sophie Organe, Joanna Segers, Leen Timmermans, Frank Vanderhoydonc, Ludo Deboel, Rita Derua, Etienne Waelkens, Ellen De Schrijver, Tine Van de Sande, Agnès Noël, Fabienne Foufelle, Guido Verhoeven,

Metabolism, Diabetes, and Cancer

Abstract 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.