ST2825, independent of MyD88, induces reactive oxygen species-dependent apoptosis in multiple myeloma cells
Myeloid differentiation factor 88 (MyD88), which is a key regulator of nuclear factor kappa B (NF-κB), plays an important role in tumorigenesis in lymphoid malignancies such as Waldenstrom's macroglobulinemia (WM). However, its biological function in multiple myeloma (MM), which is a malignant...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-07-01
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| Series: | Biochemistry and Biophysics Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580824000451 |
| _version_ | 1797272420566958080 |
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| author | Hajime Nakamura Yohei Arihara Makoto Usami Kohichi Takada |
| author_facet | Hajime Nakamura Yohei Arihara Makoto Usami Kohichi Takada |
| author_sort | Hajime Nakamura |
| collection | DOAJ |
| description | Myeloid differentiation factor 88 (MyD88), which is a key regulator of nuclear factor kappa B (NF-κB), plays an important role in tumorigenesis in lymphoid malignancies such as Waldenstrom's macroglobulinemia (WM). However, its biological function in multiple myeloma (MM), which is a malignant plasma cell disorder like WM, remains unexplored. In this article, we first demonstrated that higher expression MyD88 was significantly correlated with poor survival in patients with MM using multiple publicly available datasets. Interestingly, bioinformatic analysis also revealed that MyD88 gene alteration, which is recognized in nearly 80% of patients with WM, was extremely rare in MM. In addition, ST2825 (a specific inhibitor of MyD88) suppressed cell growth followed by apoptosis. Furthermore, ST2825 induced intracellular reactive oxygen species (ROS) in MM cells, and N-acetyl-l-cysteine, which is known as a ROS scavenger, significantly decreased the number of apoptotic MM cells evoked by ST2825 treatment. Taken together, our results indicated that ST2825 leads to ROS-dependent apoptosis in MM cells and could be an attractive therapeutic candidate for patients with MM. By highlighting the pathological mechanism of MyD88 in MM, this study also provides novel treatment strategies to conquer MM. |
| first_indexed | 2024-03-07T14:29:04Z |
| format | Article |
| id | doaj.art-6dc3db066b764e5284bcecac4dca5e4f |
| institution | Directory Open Access Journal |
| issn | 2405-5808 |
| language | English |
| last_indexed | 2024-03-07T14:29:04Z |
| publishDate | 2024-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| spelling | doaj.art-6dc3db066b764e5284bcecac4dca5e4f2024-03-06T05:27:40ZengElsevierBiochemistry and Biophysics Reports2405-58082024-07-0138101681ST2825, independent of MyD88, induces reactive oxygen species-dependent apoptosis in multiple myeloma cellsHajime Nakamura0Yohei Arihara1Makoto Usami2Kohichi Takada3Department of Medical Oncology, Sapporo Medical University School of Medicine, JapanDepartment of Medical Oncology, Sapporo Medical University School of Medicine, JapanDepartment of Medical Oncology, Sapporo Medical University School of Medicine, JapanDepartment of Medical Oncology, Sapporo Medical University School of Medicine, Japan; Corresponding author. Department of Medical Oncology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan.Myeloid differentiation factor 88 (MyD88), which is a key regulator of nuclear factor kappa B (NF-κB), plays an important role in tumorigenesis in lymphoid malignancies such as Waldenstrom's macroglobulinemia (WM). However, its biological function in multiple myeloma (MM), which is a malignant plasma cell disorder like WM, remains unexplored. In this article, we first demonstrated that higher expression MyD88 was significantly correlated with poor survival in patients with MM using multiple publicly available datasets. Interestingly, bioinformatic analysis also revealed that MyD88 gene alteration, which is recognized in nearly 80% of patients with WM, was extremely rare in MM. In addition, ST2825 (a specific inhibitor of MyD88) suppressed cell growth followed by apoptosis. Furthermore, ST2825 induced intracellular reactive oxygen species (ROS) in MM cells, and N-acetyl-l-cysteine, which is known as a ROS scavenger, significantly decreased the number of apoptotic MM cells evoked by ST2825 treatment. Taken together, our results indicated that ST2825 leads to ROS-dependent apoptosis in MM cells and could be an attractive therapeutic candidate for patients with MM. By highlighting the pathological mechanism of MyD88 in MM, this study also provides novel treatment strategies to conquer MM.http://www.sciencedirect.com/science/article/pii/S2405580824000451Myeloid differentiation factor 88ST2825Multiple myeloma |
| spellingShingle | Hajime Nakamura Yohei Arihara Makoto Usami Kohichi Takada ST2825, independent of MyD88, induces reactive oxygen species-dependent apoptosis in multiple myeloma cells Biochemistry and Biophysics Reports Myeloid differentiation factor 88 ST2825 Multiple myeloma |
| title | ST2825, independent of MyD88, induces reactive oxygen species-dependent apoptosis in multiple myeloma cells |
| title_full | ST2825, independent of MyD88, induces reactive oxygen species-dependent apoptosis in multiple myeloma cells |
| title_fullStr | ST2825, independent of MyD88, induces reactive oxygen species-dependent apoptosis in multiple myeloma cells |
| title_full_unstemmed | ST2825, independent of MyD88, induces reactive oxygen species-dependent apoptosis in multiple myeloma cells |
| title_short | ST2825, independent of MyD88, induces reactive oxygen species-dependent apoptosis in multiple myeloma cells |
| title_sort | st2825 independent of myd88 induces reactive oxygen species dependent apoptosis in multiple myeloma cells |
| topic | Myeloid differentiation factor 88 ST2825 Multiple myeloma |
| url | http://www.sciencedirect.com/science/article/pii/S2405580824000451 |
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