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

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.

journal_name

Cancer Res

journal_title

Cancer research

authors

Swinnen JV,Beckers A,Brusselmans K,Organe S,Segers J,Timmermans L,Vanderhoydonc F,Deboel L,Derua R,Waelkens E,De Schrijver E,Van de Sande T,Noël A,Foufelle F,Verhoeven G

doi

10.1158/0008-5472.CAN-04-3025

subject

Has Abstract

pub_date

2005-03-15 00:00:00

pages

2441-8

issue

6

eissn

0008-5472

issn

1538-7445

pii

65/6/2441

journal_volume

65

pub_type

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