Induction of apoptosis in a human leukemic cell line via reactive oxygen species modulation by antioxidants |
| |
| Authors: | Tullia Maraldi Cecilia Prata Diana Fiorentini Laura Zambonin Laura Landi Gabriele Hakim |
| |
| Institution: | 1. Department of Materials Science and Engineering, University of Wisconsin-Madison, 1509 University Ave., Madison, WI 53706, USA;2. Department of Engineering Physics, University of Wisconsin-Madison, Madison, WI 53706, USA;1. Laboratorio de Bioelectroquímica, Universidad de Chile, Sergio Livingstone P. 1007, Santiago, Chile;2. Laboratorio de Síntesis Orgánica y Modelamiento Molecular, Universidad de Chile, Sergio Livingstone P. 1007, Santiago, Chile;3. Departamento de Química Inorgánica y Analítica. Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Sergio Livingstone P. 1007, Santiago, Chile;1. School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan East Road of Higher Education Mega Centre, Guangzhou 510006, China;2. School of Pharmaceutical Sciences, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, China;3. Laboratory of Physical Biology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, 2019 Jialuo Road, Shanghai 201800, China;1. Molecular Biology Interdepartmental Ph.D. Program, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA;2. Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA;3. Molecular Biology Institute, Jonsson Comprehensive Cancer Center, UCLA Broad Stem Cell Center, and Mattel Children’s Hospital UCLA, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA;1. Department of Cancer Biology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA |
| |
| Abstract: | In the human acute myeloid leukemia cell line M07e, the growth factor interleukin-3 (IL-3) induces ROS formation, positively affecting Glut1-mediated glucose uptake and cell survival. The effect of IL-3 and exogenous hydrogen peroxide on cell viability seems to be mediated through inhibition of the cell death commitment, as shown by apoptotic markers such as caspase activities, apoptotic nuclei, and changes in the amount of proteins belonging to the Bcl-2 family. The pivotal role of ROS is confirmed using various antioxidants, such as EUK-134, ebselen, TEMPO, and hydroxylamine probe. In fact, these antioxidants, acting through different mechanisms, decrease glucose transport activity and cell proliferation activated by IL-3 or by low concentrations of hydrogen peroxide. Moreover, antioxidants foster programmed cell death commitment, as shown by the cited apoptotic parameters. EUK-134, a combined superoxide dismutase/catalase mimetic, opposes the effects of IL-3 and H2O2, decreasing phosphorylation levels of signaling enzymes such as Akt, Src tyrosine kinase, and ERK. Results show that ROS production induced by IL-3 can protect leukemic cells from apoptosis, the effect being counteracted by antioxidants. This mechanism may play an important role in supporting acute myeloid leukemia treatment, thus representing a novel therapeutic strategy. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
