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Tamoxifen induces toxicity, causes autophagy, and partially reverses dexamethasone resistance in Jurkat T cells
Author(s) -
TorresLópez Liliana,
Maycotte Paola,
LiñánRico Andrómeda,
LiñánRico Liliana,
DonisMaturano Luis,
DelgadoEnciso Iván,
MezaRobles Carmen,
VásquezJiménez Clemente,
HernándezCruz Arturo,
Dobrovinskaya Oxana
Publication year - 2019
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.2vma0818-328r
Subject(s) - jurkat cells , gper , biology , estrogen receptor , autophagy , cancer research , atg5 , microbiology and biotechnology , t cell , immune system , antiestrogen , apoptosis , immunology , cancer , breast cancer , biochemistry , genetics
Estrogens demonstrate biological activity in numerous organ systems, including the immune system, and exert their effects through estrogen receptors (ER) of two types: intracellular ERα and ERβ 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 ERα‐positive breast cancer, is considered as an ERα 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 ERα or ERβ. 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.