Tunicamycin promotes apoptosis in leukemia cells through ROS generation and downregulation of survivin expression
Abstract Tunicamycin (TN), one of the endoplasmic reticulum stress inducers, has been reported to inhibit tumor cell growth and exhibit anticarcinogenic activity. However, the mechanism by which TN initiates apoptosis remains poorly understood. In the present study, we investigated the effect of TN on the apoptotic pathway in U937 cells. We show that TN induces apoptosis in association with caspase-3 activation, generation of reactive oxygen species (ROS), and downregulation of survivin expression. P38 MAPK (mitogen-activated protein kinase) and the generation of ROS signaling pathway play crucial roles in TN-induced apoptosis in U937 cells. We hypothesized that TN-induced activation of p38 MAPK signaling pathway is responsible for cell death. To test this hypothesis, we selectively inhibited MAPK during treatment with TN. Our data demonstrated that inhibitor of p38 (SB), but not ERK (PD) or JNK (SP), partially maintained apoptosis during treatment with TN. Pre-treatment with NAC and GSH markedly prevented cell death, suggesting a role for ROS in this process. Ectopic expression of survivin in U937 cells attenuated TN-induced apoptosis by suppression of caspase-3 cleavage, mitochondrial membrane potential, and cytochrome c release in U937 cells. Taken together, our results show that TN modulates multiple components of the apoptotic response of human leukemia cells and raise the possibility of a novel therapeutic strategy for hematological malignancies.
Publication date: Available online 15 May 2020Source: Journal of Ginseng ResearchAuthor(s): Sirui Zhu, Xiaoli Liu, Mei Xue, Yu Li, Danhong Cai, Shijun Wang, Liang Zhang
Publication date: Available online 30 May 2020Source: Seminars in Cancer BiologyAuthor(s): Xiaohua Lu, Thomas Efferth
Publication date: Available online 30 April 2020Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Alessandra Malato, Elena Rossi, Mario Tiribelli, Francesco Mendicino, Novella Pugliese
Authors: Dong A, Yang W, Huang H, Zhou X, He Z, Yao R, Guo W Abstract Changes in histone H3 lysine 9 trimethylation (H3K9me3) may be related to the development of drug‑resistant acute myeloid leukaemia (AML); insights into the network of H3K9me3 may improve patient prognosis. Patient data were derived from the Gene Expression Omnibus (GEO) database and data from AML cells treated with chidamide, a novel benzamide chemical class of histone deacetylase inhibitor (HDACi), in vitro were derived from ChIP‑seq. Patients and AML cell data were analysed using GEO2R, GOseq, KOBAS, the STRING database and Cytoscape ...
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