Targeting Non-Apoptotic Pathways with the Cell Permeable TAT-Conjugated NOTCH1 RAM Fragment for Leukemia and Lymphoma Cells DOI Creative Commons

Ryota Uchimura,

Shinpei Nishimura,

Mari Ozaki

et al.

ACS Omega, Journal Year: 2024, Volume and Issue: 9(50), P. 49925 - 49934

Published: Dec. 2, 2024

Targeting nonapoptotic cell death offers a promising strategy for overcoming apoptosis resistance in cancer. In this study, we developed Tat-Ram13, 25-mer peptide that fuses the NOTCH1 intracellular domain fragment RAM13 with cell-penetrating HIV-1 TAT, treatment of T-cell acute lymphoblastic leukemia aberrant mutation. Tat-Ram13 significantly downregulated NOTCH1-target genes T-ALL lines. Furthermore, had potent cytotoxic effects on various human and lymphoma However, it did not affect normal lymphocytes monocytes, some subsets cells, or adherent tumor cells. This cell-selective activity was closely correlated uptake via macropinocytosis triggered rapid death. involved mitochondrial membrane depolarization extracellular release lactate dehydrogenase high-mobility group box-1 protein without activation caspase-3 cleavage PARP-1. These results suggest is mediated by plasma rupture. Moreover, alanine scanning analysis identified four critical hydrophobic amino acids essential its cytotoxicity. Consequently, these tumor-selective, death-inducing agent treating refractory lymphomas resistance.

Language: Английский

Unraveling the mechanisms of NINJ1-mediated plasma membrane rupture in lytic cell death and related diseases DOI
Jiajia Yang,

Chun Luo,

Kunbo Wang

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: 309, P. 143165 - 143165

Published: April 15, 2025

Language: Английский

Citations

0
Uncovering NINJ1 in SLE: Biomarker potential for renal and hematologic manifestations DOI
Muyuan Li, Ke Liu,

Meidong Liu

et al.

Clinica Chimica Acta, Journal Year: 2025, Volume and Issue: 574, P. 120347 - 120347

Published: May 5, 2025

Language: Английский

Citations

0
Targeting Non-Apoptotic Pathways with the Cell Permeable TAT-Conjugated NOTCH1 RAM Fragment for Leukemia and Lymphoma Cells DOI Creative Commons

Ryota Uchimura,

Shinpei Nishimura,

Mari Ozaki

et al.

ACS Omega, Journal Year: 2024, Volume and Issue: 9(50), P. 49925 - 49934

Published: Dec. 2, 2024

Targeting nonapoptotic cell death offers a promising strategy for overcoming apoptosis resistance in cancer. In this study, we developed Tat-Ram13, 25-mer peptide that fuses the NOTCH1 intracellular domain fragment RAM13 with cell-penetrating HIV-1 TAT, treatment of T-cell acute lymphoblastic leukemia aberrant mutation. Tat-Ram13 significantly downregulated NOTCH1-target genes T-ALL lines. Furthermore, had potent cytotoxic effects on various human and lymphoma However, it did not affect normal lymphocytes monocytes, some subsets cells, or adherent tumor cells. This cell-selective activity was closely correlated uptake via macropinocytosis triggered rapid death. involved mitochondrial membrane depolarization extracellular release lactate dehydrogenase high-mobility group box-1 protein without activation caspase-3 cleavage PARP-1. These results suggest is mediated by plasma rupture. Moreover, alanine scanning analysis identified four critical hydrophobic amino acids essential its cytotoxicity. Consequently, these tumor-selective, death-inducing agent treating refractory lymphomas resistance.

Language: Английский

Citations

0