Cell Death Induction by MO2455, a Novel Potential Anti-Cancer Agent in Monocytic and T-Cell Leukemia Cells
5 affiliations
- 1Department of Molecular and Genomic Biomedicine, Center for Bioinformatics and Molecular Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan
- 2Department of Pharmacy, Yasuda Women’s University, Hiroshima 731-0153, Japan
- 3Department of Chemistry and Life Science, School of Advanced Engineering, Kogakuin University, Tokyo 192-0015, Japan
- 4Department of Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan
- 5Faculty of Engineering, Kanagawa Institute of Technology, Atsugi 243-0292, Japan
Abstract
Despite advances in targeted therapies, treatment resistance and disease recurrence remain major obstacles in leukemia management. Structural modification of clinically successful kinase inhibitors represents a promising approach for discovering novel anti-leukemic agents with improved biological activities. In the present study, we investigated the anti-leukemic activity and mechanism of action of MO2455, a newly synthesized imatinib-derived compound, in monocytic leukemia U937, THP−1, and T-cell leukemia CCRF-CEM cells. MO2455 showed substantial cytotoxic activity against all three cell lines, with IC50 values of 0.83 μM, 0.43 μM, and 0.57 μM in U937, THP−1, and CCRF-CEM cells, respectively. Treatment with MO2455 induced early mitochondrial membrane depolarization, internucleosomal DNA laddering, a significant accumulation of sub−G1 population and increased Annexin V positivity, suggesting typical apoptosis without cell cycle arrest in U937 cells. MO2455 induced γ-H2AX induction and upregulated the pro-apoptotic NOXA and BBC3 genes. THP−1 and CCRF-CEM cells displayed distinct large DNA fragmentation with smearing. In PBMCs from two healthy donors, IC50 values were 0.99 and 0.60 μM, respectively, although the cells remained morphologically healthy without obvious extensive cell death. Overall, MO2455 exhibits substantial anti-leukemic activity and induces cell death through apoptosis and other mechanisms, supporting further investigation as an anti-leukemic agent.
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BibTeX
@article{velu2026cell,
title = {{Cell Death Induction by MO2455, a Novel Potential Anti-Cancer Agent in Monocytic and T-Cell Leukemia Cells}},
author = {Ankitha Vadi Velu and Kenji Matsuno and Barkha Saraswat and Osamu Ohno and Yu Yingchun and Zhao Zhenkai and Ying Tong and Takahiro Tougan and Taiki Aoshi and Takeji Takamura and Fumiaki Koizumi and Mitsuko Masutani},
journal = {Cells},
year = {2026},
month = sep,
doi = {10.3390/cells15191780},
url = {https://www.mdpi.com/2073-4409/15/19/1780},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Cell Death Induction by MO2455, a Novel Potential Anti-Cancer Agent in Monocytic and T-Cell Leukemia Cells
AU - Ankitha Vadi Velu
AU - Kenji Matsuno
AU - Barkha Saraswat
AU - Osamu Ohno
AU - Yu Yingchun
AU - Zhao Zhenkai
AU - Ying Tong
AU - Takahiro Tougan
AU - Taiki Aoshi
AU - Takeji Takamura
AU - Fumiaki Koizumi
AU - Mitsuko Masutani
PY - 2026
DA - 2026/09/30
JO - Cells
DO - 10.3390/cells15191780
UR - https://www.mdpi.com/2073-4409/15/19/1780
AB - Despite advances in targeted therapies, treatment resistance and disease recurrence remain major obstacles in leukemia management. Structural modification of clinically successful kinase inhibitors represents a promising approach for discovering novel anti-leukemic agents with improved biological activities. In the present study, we investigated the anti-leukemic activity and mechanism of action of MO2455, a newly synthesized imatinib-derived compound, in monocytic leukemia U937, THP−1, and T-cell leukemia CCRF-CEM cells. MO2455 showed substantial cytotoxic activity against all three cell lines, with IC50 values of 0.83 μM, 0.43 μM, and 0.57 μM in U937, THP−1, and CCRF-CEM cells, respectively. Treatment with MO2455 induced early mitochondrial membrane depolarization, internucleosomal DNA laddering, a significant accumulation of sub−G1 population and increased Annexin V positivity, suggesting typical apoptosis without cell cycle arrest in U937 cells. MO2455 induced γ-H2AX induction and upregulated the pro-apoptotic NOXA and BBC3 genes. THP−1 and CCRF-CEM cells displayed distinct large DNA fragmentation with smearing. In PBMCs from two healthy donors, IC50 values were 0.99 and 0.60 μM, respectively, although the cells remained morphologically healthy without obvious extensive cell death. Overall, MO2455 exhibits substantial anti-leukemic activity and induces cell death through apoptosis and other mechanisms, supporting further investigation as an anti-leukemic agent.
SN - 2073-4409
ER -