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Source: Autophagy

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Total 127 results found since Jan 2013.

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

Q6, a novel hypoxia-targeted drug, regulates hypoxia-inducible factor signaling via an autophagy-dependent mechanism in hepatocellular carcinoma.
Abstract Tumor hypoxia underlies treatment failure and yields more aggressive and metastatic cancer phenotypes. Although therapeutically targeting these hypoxic environments has been proposed for many years, to date no approaches have shown the therapeutic value to gain regulatory approval. Here, we demonstrated that a novel hypoxia-activated prodrug, Q6, exhibits potent antiproliferative efficacy under hypoxic conditions and induces caspase-dependent apoptosis in 2 hepatocellular carcinoma (HCC) cell lines, with no obvious toxicity being detected in 2 normal liver cell lines. Treatment with Q6 markedly downregula...
Source: Autophagy - November 11, 2013 Category: Cytology Authors: Liu XW, Cai TY, Zhu H, Cao J, Su Y, Hu YZ, He QJ, Yang B Tags: Autophagy Source Type: research

MTOR inhibition attenuates DNA damage and apoptosis through autophagy-mediated suppression of CREB1.
Abstract Hyperactivation of mechanistic target of rapamycin (MTOR) is a common feature of human cancers, and MTOR inhibitors, such as rapamycin, are thus becoming therapeutics in targeting certain cancers. However, rapamycin has also been found to compromise the efficacy of chemotherapeutics to cells with hyperactive MTOR. Here, we show that loss of TSC2 or PTEN enhanced etoposide-induced DNA damage and apoptosis, which was blunted by suppression of MTOR with either rapamycin or RNA interference. cAMP response element-binding protein 1 (CREB1), a nuclear transcription factor that regulates genes involved in surviv...
Source: Autophagy - November 1, 2013 Category: Cytology Authors: Wang Y, Hu Z, Liu Z, Chen R, Peng H, Guo J, Chen X, Zhang H Tags: Autophagy Source Type: research

Dual inhibition of autophagy and the AKT pathway in prostate cancer.
Abstract Genetic inactivation of PTEN through either gene deletion or mutation is common in metastatic prostate cancer, leading to activation of the phosphoinositide 3-kinase (PI3K-AKT) pathway, which is associated with poor clinical outcomes. The PI3K-AKT pathway plays a central role in various cellular processes supporting cell growth and survival of tumor cells. To date, therapeutic approaches to develop inhibitors targeting the PI3K-AKT pathway have failed in both pre-clinical and clinical trials. We showed that a novel AKT inhibitor, AZD5363, inhibits the AKT downstream pathway by reducing p-MTOR and p-RPS6KB...
Source: Autophagy - May 6, 2013 Category: Cytology Authors: Lamoureux F, Zoubeidi A Tags: Autophagy Source Type: research

Autophagy and ER stress play an essential role in the mechanism of action and drug resistance of the cyclin-dependent kinase inhibitor flavopiridol.
Abstract Chronic lymphocytic leukemia (CLL) is a mature B cell malignancy and is the most prevalent type of leukemia in adults. There is no curative therapy for this disease; however, several new agents have shown very promising results. Autophagy has not been studied in CLL and in this study we first sought to determine if autophagy was functional in CLL with classic inducers, and if this contributes to direct cytotoxicity or protection from cell death. While autophagy is activated with all classic stimuli of this process, only unfolded protein endoplasmic reticulum (ER) stress-mediated autophagy protects from ce...
Source: Autophagy - February 26, 2013 Category: Cytology Authors: Mahoney E, Byrd JC, Johnson AJ Tags: Autophagy Source Type: research

Hypertonic stress promotes autophagy and microtubule-dependent autophagosomal clusters.
Abstract Osmotic homeostasis is fundamental for most cells, which face recurrent alterations of environmental osmolality that challenge cell viability. Protein damage is a consequence of hypertonic stress, but whether autophagy contributes to the osmoprotective response is unknown. Here, we investigated the possible implications of autophagy and microtubule organization on the response to hypertonic stress. We show that hypertonicity rapidly induced long-lived protein degradation, LC3-II generation and Ptdlns3K-dependent formation of LC3- and ATG12-positive puncta. Lysosomotropic agents chloroquine and bafilomycin...
Source: Autophagy - February 4, 2013 Category: Cytology Authors: Nunes P, Ernandez T, Roth I, Qiao X, Strebel D, Bouley R, Charollais A, Ramadori P, Foti M, Meda P, Féraille E, Brown D, Hasler U 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