Ribavirin acts via multiple pathways in inhibition of leukemic cell proliferation

Anticancer Res. 2009 Jun;29(6):1971-80.

Abstract

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.

Materials and 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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites / pharmacology*
  • Apoptosis / drug effects
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects*
  • Colony-Forming Units Assay
  • Gene Expression Profiling
  • Humans
  • Leukemia / metabolism
  • Leukemia / pathology*
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ribavirin / pharmacology*
  • Signal Transduction / drug effects*
  • Tumor Cells, Cultured

Substances

  • Antimetabolites
  • RNA, Messenger
  • Ribavirin