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Myeloma

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

Leukemia volume 24, pages 843–850 (2010)Cite this article

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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.

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Acknowledgements

This work was partly supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and by grants from the Kobayashi Foundation of Innovative Cancer Chemotherapy, the Award in Aki's Memory from International Myeloma Foundation, and the Japan Leukaemia Research Fund (MT and JK).

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Authors and Affiliations

  1. Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan

    T Kobayashi, J Kuroda, M Yamamoto, N Sasaki, S Horiike & M Taniwaki

  2. Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto, Japan

    E Ashihara

  3. Department of Immunology and Immunopathology, Faculty of Medicine, Kagawa University, Kagawa, Japan

    S Oomizu & M Hirashima

  4. Division of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan

    Y Terui, A Taniyama & K Hatake

  5. Department of Gastroenterology, Kyoto Prefectural University of Medicine, Kyoto, Japan

    S Adachi & T Takagi

  6. Department of Cell Regulation, Faculty of Medicine, Kagawa University, Kagawa, Japan

    A Yamauchi

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  1. T Kobayashi
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Correspondence to J Kuroda.

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Kobayashi, T., Kuroda, J., Ashihara, E. et al. Galectin-9 exhibits anti-myeloma activity through JNK and p38 MAP kinase pathways. Leukemia 24, 843–850 (2010). https://doi.org/10.1038/leu.2010.25

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