Pro-Inflammatory Activation Suppresses TRAIL-Induced Apoptosis of Acute Myeloid Leukemia Cells
Author:
Kobyakova M. I.12, Senotov A. S.1, Krasnov K. S.1, Lomovskaya Ya. V.1, Odinokova I. V.1, Kolotova A. A.1, Ermakov A. M.1, Zvyagina A. I.1, Fadeeva I. S.1, Fetisova E. I.1, Akatov V. S.1, Fadeev R. S.1
Affiliation:
1. Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences 2. Institute of Clinical and Experimental Lymphology, Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences
Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) is a promising agent for the treatment of AML due to its specific apoptosis-inducing effect on tumor cells but not normal cells. However, the emergence of resistance in AML cells to TRAIL limits its potential as an antileukemic agent. Previously, we revealed an increase in the resistance of human AML THP-1 cells to TRAIL-induced death during their LPS-dependent proinflammatory activation and in an in vitro model of LPS-independent proinflammatory activation - in a long-term high-density cell culture. In this study, we investigated the mechanisms of this phenomenon using western blot analysis, caspase 3 enzymatic activity analysis, quantitative reverse transcription-PCR, and flow cytometry. The results showed that increased resistance to TRAIL-induced cell death of AML THP-1 cells during their pro-inflammatory activation is associated with a decrease in the surface expression of the proapototic receptors TRAIL-R1/DR4 and TRAIL-R2/DR5, as well as with an increased content of members of the IAPs family - Livin and cIAP2. The results of this article open up new insights into the role of inflammation in the formation of resistance of AML cells to the action of mediators of antitumor immunity, in particular TRAIL.
Publisher
The Russian Academy of Sciences
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