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A novel orally available seleno-purine molecule suppresses triple-negative breast cancer cell proliferation and progression to metastasis by inducing cytostatic autophagy.
Abstract Patients with triple-negative breast cancer (TNBC) often have a poor prognosis largely due to lack of effective targeted therapy. Using a library of seleno-purines coupled to a high-throughput biochemical enzymatic assays we identified a potent pharmacological enhancer of autophagy (referred herein as SLLN-15) that selectively activated cytostatic macroautophagy/autophagy in TNBC preclinical models. SLLN-15 induced a dose-dependent anti-proliferative activity in the TNBC cell lines MDA-MB-231 and BT-20 via induction of autophagy and autophagic flux. This induction was associated with a selective inhibitio...
Source: Autophagy - February 17, 2019 Category: Cytology Authors: Chang CH, Bijian K, Wernic D, Su J, da Silva SD, Yu H, Qiu D, Asslan M, Alaoui-Jamali MA Tags: Autophagy Source Type: research

BIX-01294 induces autophagy-associated cell death via EHMT2/G9a dysfunction and intracellular reactive oxygen species production.
Abstract We screened a chemical library in MCF-7 cells stably expressing green fluorescent protein (GFP)-conjugated microtubule-associated protein 1 light chain 3 (LC3) (GFP-LC3-MCF-7) using cell-based assay, and identified BIX-01294 (BIX), a selective inhibitor of euchromatic histone-lysine N-methyltransferase 2 (EHMT2), as a strong autophagy inducer. BIX enhanced formation of GFP-LC3 puncta, LC3-II, and free GFP, signifying autophagic activation. Inhibition of these phenomena with chloroquine and increasement in punctate dKeima ratio (550/438) signal indicated that BIX activated autophagic flux. BIX-induced cell...
Source: Autophagy - December 1, 2013 Category: Cytology Authors: Kim Y, Kim YS, Kim DE, Lee JS, Song JH, Kim HG, Cho DH, Jeong SY, Jin DH, Jang SJ, Seol HS, Suh YA, Lee SJ, Kim CS, Koh JY, Hwang JJ Tags: Autophagy Source Type: research

IFNB1/interferon-β-induced autophagy in MCF-7 breast cancer cells counteracts its proapoptotic function.
Abstract IFNB1/interferon (IFN)-β belongs to the type I IFNs and exerts potent antiproliferative, proapoptotic, antiangiogenic and immunemodulatory functions. Despite the beneficial effects of IFNB1 in experimental breast cancers, clinical translation has been disappointing, possibly due to induction of survival pathways leading to treatment resistance. Defects in autophagy, a conserved cellular degradation pathway, are implicated in numerous cancer diseases. Autophagy is induced in response to cancer therapies and can contribute to treatment resistance. While the type II IFN, IFNG, which in many aspects differs ...
Source: Autophagy - December 7, 2012 Category: Cytology Authors: Ambjørn M, Ejlerskov P, Liu Y, Lees M, Jäättelä M, Issazadeh-Navikas S Tags: Autophagy Source Type: research