Mimicry of a cellular low energy status blocks tumor cell anabolism and suppresses the malignant phenotype.

[en] 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.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Swinnen, J. V.

Beckers, Annelies

Brusselmans, K.

Organe, S.

Segers, J.

Timmermans, L.

Vanderhoydonc, F.

Deboel, L.

Derua, R.

Waelkens, E.

More authors (5 more)

Language :

English

Title :

Mimicry of a cellular low energy status blocks tumor cell anabolism and suppresses the malignant phenotype.

Publication date :

2005

Journal title :

Cancer Research

ISSN :

0008-5472

eISSN :

1538-7445

Publisher :

American Association for Cancer Research, Inc. (AACR), Baltimore, United States - Maryland

Volume :

Issue :

Pages :

2441-8

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 21 December 2009

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Scopus citations^®

118

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115

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100

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