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

Tamoxifen induces toxicity, causes autophagy, and partially reverses dexamethasone resistance in Jurkat T cells. J Leukoc Biol. 2019 Jan 15;: Authors: Torres-López L, Maycotte P, Liñán-Rico A, Liñán-Rico L, Donis-Maturano L, Delgado-Enciso I, Meza-Robles C, Vásquez-Jiménez C, Hernández-Cruz A, Dobrovinskaya O Abstract 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 rev...
Source: Journal of Leukocyte Biology - Category: Hematology Authors: Tags: J Leukoc Biol Source Type: research