We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Galectin-9 exhibits anti-myeloma activity through JNK and p38 MAP kinase pathways.
- Authors
Kobayashi, T.; Kuroda, J.; Ashihara, E.; Oomizu, S.; Terui, Y.; Taniyama, A.; Adachi, S.; Takagi, T.; Yamamoto, M.; Sasaki, N.; Horiike, S.; Hatake, K.; Yamauchi, A.; Hirashima, M.; Taniwaki, M.
- Abstract
Galectins constitute a family of lectins that specifically exhibit the affinity for β-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 IC50 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 NH2-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.
- Subjects
MULTIPLE myeloma; LECTINS; DRUG therapy; B cell lymphoma; APOPTOSIS
- Publication
Leukemia (08876924), 2010, Vol 24, Issue 4, p843
- ISSN
0887-6924
- Publication type
Article
- DOI
10.1038/leu.2010.25