Tamoxifen induces toxicity, causes autophagy, and partially reverses dexamethasone resistance in Jurkat T cells

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

article

Liliana Torres-López¹  Paola Maycotte³  Andrómeda Liñán-Rico⁴  Liliana Liñán-Rico¹  Luis Donis-Maturano⁵  Iván Delgado-Enciso⁶  Carmen Meza-Robles⁶  Clemente Vásquez-Jiménez¹  Arturo Hernández-Cruz⁷  Oxana Dobrovinskaya¹ 

[1] University Center for Biomedical Research, University of Colima;Faculty for Chemical Sciences, University of Colima;CONACYT-Biomedical Research Center of the East, Mexican Social Security Institute;CONACYT-University Center for Biomedical Research, University of Colima;Ensenada Biomedical Innovation Department, Center for Scientific Research and Higher Education;Medical School, University of Colima and Cancerology Institute of Colima State, Health Services;National Laboratory of Channelopathies (LaNCa), National Autonomous University of Mexico;Department of Cognitive Neuroscience-Institute of Cellular Physiology, National Autonomous University of Mexico

关键词: tamoxifen;    Jurkat cells;    estrogen receptors;    GPER;    autophagy;    apoptosis;    cell cycle;    proliferation;    glucocorticoid resistance;   

DOI  :  10.1002/JLB.2VMA0818-328R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Estrogens demonstrate biological activity in numerous organ systems, including the immune system, and exert their effects through estrogen receptors (ER) of two types: intracellular ER? and ER? that activate transcriptional factors and membrane G protein-coupled ER GPER. The latter is capable to mediate fast activation of cytosolic signaling pathways, influencing transcriptional events in response to estrogens. Tamoxifen (TAM), widely used in chemotherapy of ER?-positive breast cancer, is considered as an ER? antagonist and GPER agonist. TAM was shown to possess “off-target” cytotoxicity, not related to ER in various tumor types. The present work was designed to study biological effects of TAM on the glucocorticoid (GC)-resistant cell line Jurkat, derived from acute lymphoblastic leukemia of T lineage (T-ALL). We have shown that T-ALL cell lines, in contrast to healthy T cells, express only GPER, but not ER? or ER?. TAM compromised mitochondrial function and reduced the viability and proliferation of Jurkat cells. Additionally, TAM induced autophagy in a GPER-dependent manner. Gene expression profiling revealed the up-regulation of autophagy-related gene ATG5. Interestingly, TAM sensitized Jurkat cells to dexamethasone (DEX) treatment, which may be related to its capacity to cause autophagy. We suggest that TAM-based adjuvant therapy may represent a novel strategy in T-ALL patients handling.

【 授权许可】

CC BY