Galectin-9 exhibits anti-myeloma activity through JNK and p38 MAP kinase pathways

Leukemia. 2010 Apr;24(4):843-50. doi: 10.1038/leu.2010.25. Epub 2010 Mar 4.


Galectins constitute a family of lectins that specifically exhibit the affinity for beta-galactosides and modulate various biological events. Galectin-9 is a tandem-repeat type galectin with two carbohydrate recognition domains and has recently been shown to have an anti-proliferative effect on cancer cells. We investigated the effect of recombinant protease-resistant galectin-9 (hGal9) on multiple myeloma (MM). In vitro, hGal9 inhibited the cell proliferation of five myeloma cell lines examined, including a bortezomib-resistant subcell line, with IC(50) between 75.1 and 280.0 nM, and this effect was mediated by the induction of apoptosis with the activation of caspase-8, -9, and -3. hGal9-activated Jun NH(2)-terminal kinase (JNK) and p38 MAPK signaling pathways followed by H2AX phosphorylation. Importantly, the inhibition of either JNK or p38 MAPK partly inhibited the anti-proliferative effect of hGal9, indicating the crucial role of these pathways in the anti-MM effect of hGal9. hGal9 also induced cell death in patient-derived myeloma cells, some with poor-risk factors, such as chromosomal deletion of 13q or translocation t(4;14)(p16;q32). Finally, hGal9 potently inhibited the growth of human myeloma cells xenografted in nude mice. These suggest that hGal9 is a new therapeutic target for MM that may overcome resistance to conventional chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Blotting, Western
  • Boronic Acids / pharmacology
  • Bortezomib
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Galectins / pharmacology*
  • Gene Expression Profiling
  • Humans
  • JNK Mitogen-Activated Protein Kinases / genetics
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • MAP Kinase Kinase Kinases / genetics
  • MAP Kinase Kinase Kinases / metabolism*
  • Mice
  • Mice, Nude
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology
  • Mutation / genetics
  • Oligonucleotide Array Sequence Analysis
  • Phosphorylation
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Pyrazines / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Recombinant Proteins / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects*
  • Whole-Body Irradiation
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Boronic Acids
  • Galectins
  • LGALS9 protein, human
  • Proto-Oncogene Proteins
  • Pyrazines
  • RNA, Messenger
  • Recombinant Proteins
  • Bortezomib
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinases
  • MAP3K8 protein, human