Mimicry of a cellular low energy status blocks tumor cell anabolism and suppresses the malignant phenotype.
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.
Swinnen
Johannes V
JV
Laboratory for Experimental Medicine and Endocrinology, University of Leuven, Leuven, Belgium. johan.swinnen@med.kuleuven.ac.be
Beckers
Annelies
A
Brusselmans
Koen
K
Organe
Sophie
S
Segers
Joanna
J
Timmermans
Leen
L
Vanderhoydonc
Frank
F
Deboel
Ludo
L
Derua
Rita
R
Waelkens
Etienne
E
De Schrijver
Ellen
E
Van de Sande
Tine
T
Noël
Agnès
A
Foufelle
Fabienne
F
Verhoeven
Guido
G
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
D012263:Ribonucleosides; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D000249:Adenosine Monophosphate; C011651:acadesine; D000263:Adenylate Kinase; C031143:AICA ribonucleotide