T315 Decreases Acute Myeloid Leukemia Cell Viability through a Combination of Apoptosis Induction and Autophagic Cell Death
Abstract
:1. Introduction
2. Results
2.1. T315 Increases Apoptotic Cells and Reduces Viability of Acute Myeloid Leukemia (AML) Cell Lines and Primary Leukemia Cells from AML Patients
2.2. T315 Induces Down-Regulation of Protein Kinase B (Akt) and Phosphorylated Akt in AML Cell Lines
2.3. T315 Induces Apoptosis, Caspase Activation and Poly-ADP-Ribose Polymerase (PARP) Cleavage in AML Cell Lines
2.4. T315 Induces Autophagic Cell Death in AML Cell Lines
2.5. T315-Mediated Cytotoxicity Is Rescued by Combination of an Apoptosis Inhibitor and an Autophagy Inhibitor
2.6. T315 Slows the Growth of THP-1 Xenografts and Prolongs the Survival of Tumor-Bearing Athymic Nude Mice
3. Discussion
4. Materials and Methods
4.1. Cells and Culture Conditions
4.2. Reagents
4.3. MTS Assay
4.4. Cell Viability and Apoptosis Assay by Flow Cytometry
4.5. Western Blotting
4.6. Analysis of Caspase-3 Activity
4.7. In Vivo Therapeutic Efficacy Evaluation of T315 in the THP-1 Xenograft Model
4.8. Statistical Analysis
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
AML | acute myeloid leukemia |
DMSO | dimethyl sulfoxide |
FITC | fluorescein isothiocyanate |
HRP | horseradish peroxidase |
ILK | integrin-linked kinase |
PARP | poly-ADP-ribose polymerase |
PI | propidium iodide |
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Chiu, C.-F.; Weng, J.-R.; Jadhav, A.; Wu, C.-Y.; Sargeant, A.M.; Bai, L.-Y. T315 Decreases Acute Myeloid Leukemia Cell Viability through a Combination of Apoptosis Induction and Autophagic Cell Death. Int. J. Mol. Sci. 2016, 17, 1337. https://doi.org/10.3390/ijms17081337
Chiu C-F, Weng J-R, Jadhav A, Wu C-Y, Sargeant AM, Bai L-Y. T315 Decreases Acute Myeloid Leukemia Cell Viability through a Combination of Apoptosis Induction and Autophagic Cell Death. International Journal of Molecular Sciences. 2016; 17(8):1337. https://doi.org/10.3390/ijms17081337
Chicago/Turabian StyleChiu, Chang-Fang, Jing-Ru Weng, Appaso Jadhav, Chia-Yung Wu, Aaron M. Sargeant, and Li-Yuan Bai. 2016. "T315 Decreases Acute Myeloid Leukemia Cell Viability through a Combination of Apoptosis Induction and Autophagic Cell Death" International Journal of Molecular Sciences 17, no. 8: 1337. https://doi.org/10.3390/ijms17081337