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

Abstract：

: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.

journal_name

Leukemia

journal_title

Leukemia

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

doi

10.1038/leu.2010.25

subject

Has Abstract

pub_date

2010-04-01 00:00:00

pages

843-50

issue

4

eissn

0887-6924

issn

1476-5551

pii

leu201025

journal_volume

24

pub_type

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