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https://www.readbyqxmd.com/read/28445146/autophagy-and-mitophagy-in-the-context-of-doxorubicin-induced-cardiotoxicity
#1
REVIEW
Navid Koleini, Elissavet Kardami
Doxorubicin (Dox) is a cytotoxic drug widely incorporated in various chemotherapy protocols. Severe side effects such as cardiotoxicity, however, limit Dox application. Mechanisms by which Dox promotes cardiac damage and cardiomyocyte cell death have been investigated extensively, but a definitive picture has yet to emerge. Autophagy, regarded generally as a protective mechanism that maintains cell viability by recycling unwanted and damaged cellular constituents, is nevertheless subject to dysregulation having detrimental effects for the cell...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445132/targeting-autophagic-cancer-stem-cells-to-reverse-chemoresistance-in-human-triple-negative-breast-cancer
#2
Guilhem Bousquet, Morad El Bouchtaoui, Tan Sophie, Christophe Leboeuf, Cédric de Bazelaire, Philippe Ratajczak, Sylvie Giacchetti, Anne de Roquancourt, Philippe Bertheau, Laurence Verneuil, Jean-Paul Feugeas, Marc Espié, Anne Janin
There is growing evidence for the role of cancer stem-cells in drug resistance, but with few in situ studies on human tumor samples to decipher the mechanisms by which they resist anticancer agents.Triple negative breast cancer (TNBC) is the most severe sub-type of breast cancer, occurring in younger women and associated with poor prognosis even when treated at a localized stage.We investigated here the relationship between complete pathological response after chemotherapy and breast cancer stem-cell characteristics in pre-treatment biopsies of 78 women with triple negative breast carcinoma (TNBC)...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28444898/an-isoquinolin-1-2h-imine-derivative-induces-cell-death-via-generation-of-reactive-oxygen-species-and-activation-of-jnk-in-human-a549-cancer-cells
#3
Jing Liu, Tongyang Liu, Hanchuan Mou, Shuting Jia, Chao Huang, Shengjiao Yan, Jun Lin, Ying Luo, Jihong Zhang
BACKGROUND: Compound11-benzoyl-10-chloro-7,9-difluoro-6-imino-2,3,4,6-tetrahydro-1H-pyrimido[1,2-b]isoquinoline-8-carbonitrile (HC6h) is a novel polyhalo 1,3-diazaheterocycle fused isoquinolin-1(2H)-imines derivative, which displays good anticancer activity and low toxicity in vivo. However, the underlying anticancer mechanisms have not previously been identified. METHODS: The proliferation of A549 was assessed by MTT assay. The reactive oxygen species (ROS) level was assessed in A549 with a H2 DCFDA probe...
April 26, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28442482/a-bag3-coding-variant-in-mice-determines-susceptibility-to-ischemic-limb-muscle-myopathy-by-directing-autophagy
#4
Joseph M McClung, Timothy J McCord, Terence E Ryan, Cameron A Schmidt, Thomas D Green, Kevin W Southerland, Jessica L Reinardy, Sarah B Mueller, Talaignair N Venkatraman, Christopher D Lascola, Sehoon Keum, Douglas A Marchuk, Espen E Spangenburg, Ayotunde O Dokun, Brian H Annex, Christopher D Kontos
Background -Critical limb ischemia (CLI) is a manifestation of peripheral artery disease (PAD) that carries significant mortality and morbidity risk in humans, although its genetic determinants remain largely unknown. We previously discovered two overlapping quantitative trait loci (QTL) in mice, Lsq-1 and Civq-1, that affected limb muscle survival and stroke volume following femoral artery or middle cerebral artery ligation, respectively. Here we report that a Bag3 variant (Ile81Met) segregates with tissue protection from hindlimb ischemia (HLI)...
April 25, 2017: Circulation
https://www.readbyqxmd.com/read/28440459/hypoxia-induced-mir-210-promoter-demethylation-enhances-proliferation-autophagy-and-angiogenesis-of-schwannoma-cells
#5
Zhengguang Wang, Mingsi Deng, Zhendong Liu, Song Wu
Hypoxia, a dominant feature in cancer occurrence and evolution, exists throughout the progression of most malignant tumors. This study focused on the mechanism of hypoxia-induced miR-210 upregulation, and the miR-210 functions in schwannoma. We detected microvascular density, vascular endothelial growth factor (VEGF) and miR-210 expression levels using schwannoma tissue mciroarray. The results showed that miR-210 expression was significantly associated with VEGF. Moreover, the cytological tests showed that hypoxia induced miR-210 expression, while reduce ephrin-A3 expression...
May 2017: Oncology Reports
https://www.readbyqxmd.com/read/28440448/modified-panax-ginseng-extract-regulates-autophagy-by-ampk-signaling-in-a549-human-lung-cancer-cells
#6
Hwa-Seung Yoo, Jung Min Kim, Eunbi Jo, Chong-Kwan Cho, Seung-Yeul Lee, Hwan Su Kang, Min-Goo Lee, Pei-Ying Yang, Ik-Soon Jang
Panax ginseng has been used worldwide as a traditional medicine for the treatment of cancer and other diseases. The antiproliferative activity of ginseng has been increased after enzymatic processing of ginseng saponin, which may result in the accumulation of minor saponins, such as Rh2, Rg3, compound K and protopanaxatriol type (PPT) in modified regular ginseng extract (MRGX). In the present study, the anticancer activity and the associated mechanisms of MRGX were investigated using A549 human lung cancer cells...
April 20, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28440437/autophagy-related-protein-12-associates-with-anti-apoptotic-b-cell-lymphoma-2-to-promote-apoptosis-in-gentamicin-induced-inner-ear-hair-cell-loss
#7
Xiaofeng Ma, Yongze Liu, Waqas Muhammad, Dingding Liu, Junguo Wang, Han Zhou, Xia Gao, Xiaoyun Qian
The aim of the present study was to investigate the underlying mechanisms of autophagy in a gentamicin (GM)-induced ototoxic model, and to establish whether the blocking of autophagy significantly increases the survival of inner ear hair cells. Cochleae were carefully dissected from four day‑old C57BL/6J mice and randomly divided into three groups prior to explant culture: Control (culture medium), GM‑treated (culture medium + GM) and GM + 3-methyladenine (3-MA; culture medium + GM + 3‑MA). Transmission electron microscopy, immunofluorescence and western blotting were performed to observe the expression of the autophagy protein microtubule‑associated protein 1A/B‑light chain 3 in explant cultures treated with GM and the autophagy inhibitor 3‑MA...
April 11, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28437526/prominin-1-is-a-novel-regulator-of-autophagy-in-the-human-retinal-pigment-epithelium
#8
Sujoy Bhattacharya, Jinggang Yin, Christina S Winborn, Qiuhua Zhang, Junming Yue, Edward Chaum
Purpose: Prominin-1 (Prom1) is a transmembrane glycoprotein, which is expressed in stem cell lineages, and has recently been implicated in cancer stem cell survival. Mutations in the Prom1 gene have been shown to disrupt photoreceptor disk morphogenesis and cause an autosomal dominant form of Stargardt-like macular dystrophy (STGD4). Despite the apparent structural role of Prom1 in photoreceptors, its role in other cells of the retina is unknown. The purpose of this study is to investigate the role of Prom1 in the highly metabolically active cells of the retinal pigment epithelium (RPE)...
April 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28435839/the-frequency-of-yeast-psi-prion-formation-is-increased-during-chronological-ageing
#9
Shaun H Speldewinde, Chris M Grant
Ageing involves a time-dependent decline in a variety of intracellular mechanisms and is associated with cellular senescence. This can be exacerbated by prion diseases which can occur in a sporadic manner, predominantly during the later stages of life. Prions are infectious, self-templating proteins responsible for several neurodegenerative diseases in mammals and several prion-forming proteins have been found in yeast. We show here that the frequency of formation of the yeast [PSI(+) ] prion, which is the altered form of the Sup35 translation termination factor, is increased during chronological ageing...
March 27, 2017: Microbial Cell
https://www.readbyqxmd.com/read/28435159/ifitm3-inhibits-virus-triggered-induction-of-type-i-interferon-by-mediating-autophagosome-dependent-degradation-of-irf3
#10
Li-Qun Jiang, Tian Xia, Yun-Hong Hu, Ming-Shun Sun, Shuang Yan, Cao-Qi Lei, Hong-Bing Shu, Ji-Hua Guo, Yu Liu
Interferon-induced transmembrane protein 3 (IFITM3) is a restriction factor that can be induced by viral infection and interferons (IFNs). It inhibits the entry and replication of many viruses, which are independent of receptor usage but dependent on processes that occur in endosomes. In this study, we demonstrate that IFITM3 plays important roles in regulating the RNA-virus-triggered production of IFN-β in a negative-feedback manner. Overexpression of IFITM3 inhibited Sendai virus-triggered induction of IFN-β, whereas knockdown of IFITM3 had the opposite effect...
April 24, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28433512/effect-of-1-2-3-triazole-salts-non-classical-bioisosteres-of-miltefosine-on-leishmania-amazonensis
#11
Pedro H F Stroppa, Luciana M R Antinarelli, Arturene M L Carmo, Jacy Gameiro, Elaine S Coimbra, Adilson D da Silva
Here, we report the effect of new non-classical bioisosteres of miltefosine on Leishmania amazonensis. Fifteen compounds were synthesized and the compound dhmtAc, containing an acetate anion, a side chain of 10 carbon atoms linked to N-1 and a methyl group linked to N-3, showed high and selective biological activity against L. amazonensis. On the intracellular amastigotes, stages of the parasite related to human disease, the IC50 values were near or similar to the 1.0μM (0.9, 0.8 and 1.0μM on L. amazonensis-WT, and two transgenic L...
March 28, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28433067/chloroquine-and-hydroxychloroquine-inhibit-bladder-cancer-cell-growth-by-targeting-basal-autophagy-and-enhancing-apoptosis
#12
Yi-Chia Lin, Ji-Fan Lin, Sheng-I Wen, Shan-Che Yang, Te-Fu Tsai, Hung-En Chen, Kuang-Yu Chou, Thomas I-Sheng Hwang
Chloroquine (CQ) and hydroxychloroquine (HCQ), two antimalarial drugs, are suggested to have potential anticancer properties. in the present study, we investigated the effects of CQ and HCQ on cell growth of bladder cancer with emphasis on autophagy inhibition and apoptosis induction in vitro. The results showed that CQ and HCQ inhibited the proliferation of multiple human bladder cell lines (including RT4, 5637, and T24) in a time- and dose-dependent fashion, especially in advanced bladder cancer cell lines (5637 and T24) compared to immortalized uroepithelial cells (SV-Huc-1) or other reference cancer cell lines (PC3 and MCF-7)...
May 2017: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/28432280/small-molecules-targeting-histone-demethylase-genes-kdms-inhibit-growth-of-temozolomide-resistant-glioblastoma-cells
#13
Barbara Banelli, Antonio Daga, Alessandra Forlani, Giorgio Allemanni, Daniela Marubbi, Maria Pia Pistillo, Aldo Profumo, Massimo Romani
In glioblastoma several histone demethylase genes (KDM) are overexpressed compared to normal brain tissue and the development of Temozolomide (TMZ) resistance is accompanied by the transient further increased expression of KDM5A and other KDMs following a mechanism that we defined as "epigenetic resilience". We hypothesized that targeting KDMs may kill the cells that survive the cytotoxic therapy.We determined the effect of JIB 04 and CPI-455, two KDM inhibitors, on glioblastoma cells and found that both molecules are more effective against TMZ-resistant rather than native cells...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28431397/sensitization-of-tamoxifen-resistant-breast-cancer-cells-by-z-ligustilide-through-inhibiting-autophagy-and-accumulating-dna-damages
#14
Hongyi Qi, Zhuyun Jiang, Chengqiang Wang, Yi Yang, Li Li, Hui He, Zanyang Yu
Autophagy plays a pro-survival role in the tamoxifen-resistant breast cancer cells. Herein we found that autophagy was concomitantly induced in tamoxifen-resistant MCF-7 (MCF-7TR5) cells through the dissociation of Bcl-2 from Beclin 1 and subsequent enhancement of interaction among the ATG14-Beclin1-PI3KC3 complex. Moreover, higher level of DNA damage was observed in MCF-7TR5 cells with the decreased BRCA1 and RAD51 level and the increased Ku80 level. Interestingly, Nur77 was selectively degraded by autophagy, which causes the release of Ku80 from the Nur77-Ku80 complex, resulting in the increase of the DNA binding of Ku80 and DNA-PKcs...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28431282/the-role-of-pharmacologic-modulation-of-autophagy-on-anal-cancer-development-in-an-hpv-mouse-model-of-carcinogenesis
#15
Brooks L Rademacher, Kristina A Matkowskyj, Louise M Meske, Alexis Romero, Hana Sleiman, Evie H Carchman
Autophagy is an intracellular, catabolic process that maintains cellular health. We examined the response of pharmacologic modulation of autophagy in an HPV mouse model of anal carcinogenesis. K14E6/E7 mice were treated with the topical carcinogen DMBA weekly and assessed for tumors over 20 weeks. Concurrently, they were given either chloroquine or BEZ235, to inhibit or induce autophagy, respectively. Time to tumor onset was examined. Immunofluorescence (IF) was performed for LC3β and p62 to examine autophagy...
April 18, 2017: Virology
https://www.readbyqxmd.com/read/28428258/deletion-of-inositol-requiring-enzyme-1%C3%AE-in-podocytes-disrupts-glomerular-capillary-integrity-and-autophagy
#16
Daniel Robert Kaufman, Joan Papillon, Louise Larose, Takao Iwawaki, Andrey V Cybulsky
Inositol-requiring enzyme-1α (IRE1α) is an endoplasmic reticulum (ER)-transmembrane endoribonuclease-kinase, which plays an essential function in extraembryonic tissues during normal development, and is activated during ER stress. To address the functional role of IRE1α in glomerular podocytes, we produced podocyte-specific IRE1α deletion mice. In male mice, deletion of IRE1α in podocytes resulted in albuminuria beginning at 5 months of age, and worsening with time. Electron microscopy revealed focal podocyte foot process effacement in 9-month old male IRE1α deletion mice, as well as microvillous transformation of podocyte plasma membranes...
April 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28427237/oxidative-dna-double-strand-breaks-and-autophagy-in-the-antitumor-effect-of-sterically-hindered-platinum-ii-complexes-in-nsclcs
#17
Feihong Chen, Xinyi Wang, Xiufeng Jin, Jian Zhao, Shaohua Gou
A series of novel platinum(II) complexes with (1R,2R)-N1,N2-diisobutyl-1,2-diaminocyclohexane as a carrier ligand, while N1,N2-diisobutyl moiety serving as steric hindrance were designed, synthesized and characterized. The in vitro biological assays demonstrated that complex 3 had increased cytotoxicity against lung cancer cells, especially non-small-cell lung cancer (NSCLC) compared to its mono-substituted complex 3a, indicating that the sterically hindered alkyl moieties have significant influences on its antitumor property...
March 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424968/visualization-of-reticulophagy-in-living-cells-using-an-endoplasmic-reticulum-targeted-p62-mutant
#18
Liang Wang, Lei Liu, Lingsong Qin, Qingming Luo, Zhihong Zhang
Reticulophagy is a type of selective autophagy in which protein aggregate-containing and/or damaged endoplasmic reticulum (ER) fragments are engulfed for lysosomal degradation, which is important for ER homeostasis. Several chemical drugs and mutant proteins that promote protein aggregate formation within the ER lumen can efficiently induce reticulophagy in mammalian cells. However, the exact mechanism and cellular localization of reticulophagy remain unclear. In this report, we took advantage of the self-oligomerization property of p62/SQSTM1, an adaptor for selective autophagy, and developed a novel reticulophagy system based on an ER-targeted p62 mutant to investigate the process of reticulophagy in living cells...
April 13, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28423511/atm-kinase-sustains-breast-cancer-stem-like-cells-by-promoting-atg4c-expression-and-autophagy
#19
Martina Antonelli, Flavie Strappazzon, Ivan Arisi, Rossella Brandi, Mara D'Onofrio, Manolo Sambucci, Gwenola Manic, Ilio Vitale, Daniela Barilà, Venturina Stagni
The efficacy of Ataxia-Telangiectasia Mutated (ATM) kinase signalling inhibition in cancer therapy is tempered by the identification of new emerging functions of ATM, which suggests that the role of this protein in cancer progression is complex. We recently demonstrated that this tumor suppressor gene could act as tumor promoting factor in HER2 (Human Epidermal Growth Factor Receptor 2) positive breast cancer. Herein we put in evidence that ATM expression sustains the proportion of cells with a stem-like phenotype, measured as the capability to form mammospheres, independently of HER2 expression levels...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422956/chronic-activation-of-ppar%C3%AE-with-fenofibrate-reduces-autophagic-proteins-in-the-liver-of-mice-independent-of-fgf21
#20
Eunjung Jo, Songpei Li, Qingning Liang, Xinmei Zhang, Hao Wang, Terence P Herbert, Trisha A Jenkins, Aimin Xu, Ji-Ming Ye
Autophagy is a catabolic mechanism to degrade cellular components to maintain cellular energy levels during starvation, a condition where PPARα may be activated. Here we report a reduced autophagic capacity in the liver following chronic activation of PPARα with fenofibrate (FB) in mice. Chronic administration of the PPARα agonist FB substantially reduced the levels of multiple autophagy proteins in the liver (Atg3, Agt4B, Atg5, Atg7 and beclin 1) which were associated with a decrease in the light chain LC3II/LC3I ratio and the accumulation of p62...
2017: PloS One
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