title: 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.
authors.affiliation: Laboratory for Experimental Medicine and Endocrinology, University of Leuven, Leuven, Belgium. johan.swinnen@med.kuleuven.ac.be
authors.forename: Johannes V
authors.initials: JV
authors.lastname: Swinnen
authors.forename: Annelies
authors.initials: A
authors.lastname: Beckers
authors.forename: Koen
authors.initials: K
authors.lastname: Brusselmans
authors.forename: Sophie
authors.initials: S
authors.lastname: Organe
authors.forename: Joanna
authors.initials: J
authors.lastname: Segers
authors.forename: Leen
authors.initials: L
authors.lastname: Timmermans
authors.forename: Frank
authors.initials: F
authors.lastname: Vanderhoydonc
authors.forename: Ludo
authors.initials: L
authors.lastname: Deboel
authors.forename: Rita
authors.initials: R
authors.lastname: Derua
authors.forename: Etienne
authors.initials: E
authors.lastname: Waelkens
authors.forename: Ellen
authors.initials: E
authors.lastname: De Schrijver
authors.forename: Tine
authors.initials: T
authors.lastname: Van de Sande
authors.forename: Agnès
authors.initials: A
authors.lastname: Noël
authors.forename: Fabienne
authors.initials: F
authors.lastname: Foufelle
authors.forename: Guido
authors.initials: G
authors.lastname: Verhoeven
mesh_terms: D000249:Adenosine Monophosphate / Q000378:metabolism; D000263:Adenylate Kinase / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D040761:Biomimetic Materials / Q000378:metabolism / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012263:Ribonucleosides / Q000378:metabolism / Q000494:pharmacology*; D012265:Ribonucleotides / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D012263:Ribonucleosides; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D000249:Adenosine Monophosphate; C011651:acadesine; D000263:Adenylate Kinase; C031143:AICA ribonucleotide