Ribavirin acts via multiple pathways in inhibition of leukemic cell proliferation.
The aim of this study was to elucidate the anticancer activity of Ribavirin, an antiviral drug and a known inhibitor of inositide-5'-monophosphate dehydrogenase.


METHODS
Using human cancer cell lines, the potential of the drug to inhibit growth and induce the apoptotic and differentiation pathways was investigated by cytological methods. The effect exerted upon gene expression was studied in K562 cells by Q-PCR.


RESULTS
Treatment with Ribavirin resulted in a significant growth inhibition (IC(50)=15 microM) via activating apoptosis and the differentiation pathway in K562 cells. It also modulated the expression of about 60 out of 85 genes having roles in cell proliferation, purine biosynthesis, translation initiation, oncogenic signaling and cell survival (p<0.05).


CONCLUSIONS
Ribavirin is a potent anticancer agent, being a strong inducer of apoptosis and a moderate inducer of differentiation in K562 cells. These effects are mediated through the modulation of key molecular and metabolic pathways.
Kökény
Szabolcs
S
National Institute of Oncology, Department of Molecular Genetics, H-1122 Budapest, Hungary.
Papp
János
J
Weber
George
G
Vaszkó
Tibor
T
Carmona-Saez
Pedro
P
Oláh
Edith
E
D000963:Antimetabolites / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D003114:Colony-Forming Units Assay; D020869:Gene Expression Profiling; D006801:Humans; D007938:Leukemia / Q000378:metabolism / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012254:Ribavirin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D000963:Antimetabolites; D012333:RNA, Messenger; D012254:Ribavirin