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Autophagy and cancer

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https://www.readbyqxmd.com/read/28238819/alkylphospholipids-an-update-on-molecular-mechanisms-and-clinical-relevance
#1
REVIEW
Pablo Ríos-Marco, Carmen Marco, Xiomara Gálvez, Jose M Jiménez-López, María P Carrasco
Alkylphospholipid (APL) represent a new class of drugs which do not interact directly with DNA but act on the cell membrane where they accumulate and interfere with lipid metabolism and signalling pathways. This review summarizes the mode of action at the molecular level of these compounds. In this sense, a diversity of mechanisms has been suggested to explain the actions of clinically-relevant APLs, in particular, in cancer treatment. One consistently reported finding is that APLs reduce the biosynthesis of phosphatidylcholine (PC) by inhibiting the rate-limiting enzyme CTP:phosphocholine cytidylyltransferase (CT)...
February 23, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28237877/osimertinib-induces-autophagy-and-apoptosis-via-reactive-oxygen-species-generation-in-non-small-cell-lung-cancer-cells
#2
Zheng-Hai Tang, Wen-Xiang Cao, Min-Xia Su, Xiuping Chen, Jin-Jian Lu
Osimertinib (OSI), also known as AZD9291, is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has been approved for the treatment of non-small cell lung cancer (NSCLC) patients harboring EGFR T790M mutation. Herein, we indicated for the first time that OSI increased the accumulations of cytoplasmic vacuoles, the expression of phosphatidylethanolamine-modified microtubule-associated protein light-chain 3 (LC3-II), and the formation of GFP-LC3 puncta in various cancer cells...
February 22, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28237114/monitoring-autophagic-responses-in-caenorhabditis-elegans
#3
M E Papandreou, N Tavernarakis
Autophagy, from the Greek auto (self) and phagy (eating), is a self-degradative process critical for eukaryotic cell homeostasis. Its rapidly responsive, highly dynamic nature renders this process essential for adapting to and offsetting acute/harsh conditions such as starvation, organelle dysfunction, and deoxyribonucleic acid (DNA) damage. Autophagy involves an intricate network of interacting factors with multiple levels of control. Importantly, dysregulation of autophagy has been linked to numerous debilitating pathologies, including cancer and neurodegenerative conditions in humans...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28237108/long-lived-protein-degradation-during-autophagy
#4
N Dupont, C Leroy, A Hamaï, P Codogno
Macroautophagy, a major lysosomal degradative pathway for cytoplasmic components, is a process that can be stimulated in response to many stressful situations including cancer treatment. The central autophagic organelle is the autophagosome, a double-membrane-bound vacuole that sequesters cytoplasmic material. The ultimate destiny of the autophagosome is fusion with the lysosomal compartment, where cargo, including proteins, is degraded. Here, we report a method to measure the lysosomal degradation of long-lived proteins along the autophagic pathway...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28237106/methods-to-study-chaperone-mediated-autophagy
#5
E Arias
Chaperone-mediated autophagy (CMA), a selective form of degradation of cytosolic proteins in lysosomes, contributes to maintenance of proteostasis and to the cellular adaptation to stress. CMA substrates are selectively recognized and delivered by a cytosolic chaperone to the lysosomal surface, where, upon unfolding, they are internalized through a membrane translocation complex. Defective or dysfunctional CMA has been associated with human pathologies such as neurodegeneration, cancer, immunodeficiency, or diabetes, increasing the overall interest in methods to monitor this selective autophagic pathway...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28237099/assessment-of-glycolytic-flux-and-mitochondrial-respiration-in-the-course-of-autophagic-responses
#6
V Sica, J M Bravo-San Pedro, F Pietrocola, V Izzo, M C Maiuri, G Kroemer, L Galluzzi
Autophagy is an evolutionarily conserved process that mediates prominent homeostatic functions, both at the cellular and organismal level. Indeed, baseline autophagy not only ensures the disposal of cytoplasmic entities that may become cytotoxic upon accumulation, but also contributes to the maintenance of metabolic fitness in physiological conditions. Likewise, autophagy plays a fundamental role in the cellular and organismal adaptation to homeostatic perturbations of metabolic, physical, or chemical nature...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28237097/magnetic-resonance-spectroscopy-to-study-glycolytic-metabolism-during-autophagy
#7
Y-L Chung, M O Leach, T R Eykyn
Cancer cells undergoing starvation- and treatment-induced autophagy were found to exhibit reduced intracellular lactate, reduced rates of steady-state lactate excretion and reduced real-time pyruvate-lactate exchange rates, indicating that glycolytic metabolism was altered in autophagic cells. In this chapter, we describe the technical details of the use of (1)H-magnetic resonance spectroscopy (MRS) to measure endogenous cellular concentrations of lactate and glucose in autophagic cells and tissues, how to measure the rate of steady-state lactate excretion and glucose uptake by (1)H-MRS in autophagic cells, and details of the real-time measurement of [1-(13)C] pyruvate to lactate exchange in autophagic cells by (13)C-MRS-DNP (dynamic nuclear polarization)...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28237096/a-molecular-reporter-for-monitoring-autophagic-flux-in-nervous-system-in-vivo
#8
K Castillo, V Valenzuela, M Oñate, C Hetz
The relevance of autophagy in neuronal health has been extensively reported in a plethora of conditions affecting the nervous system, such as neurodegenerative diseases, cancer, diabetes, and tissue injury, where altered autophagic activity may contribute to the pathological process. Autophagy is a dynamic pathway involving the formation of a membrane surrounding and enclosing cargoes that are delivered to lysosomal compartments for degradation. Cargoes can include large protein aggregates, organelles, or even pathogens...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28236767/triggering-autophagic-cell-death-with-a-di-manganese-ii-developmental-therapeutic
#9
Creina Slator, Zara Molphy, Vickie McKee, Andrew Kellett
There is an unmet need for novel metal-based chemotherapeutics with alternative modes of action compared to clinical agents such as cisplatin and metallo-bleomycin. Recent attention in this field has focused on designing intracellular ROS-mediators as powerful cytotoxins of human cancers and identifying potentially unique toxic mechanisms underpinning their utility. Herein, we report the developmental di-manganese(II) therapeutic [Mn2(μ-oda)(phen)4(H2O)2][Mn2(μ-oda)(phen)4(oda)2]·4H2O (Mn-Oda) induces autophagy-promoted apoptosis in human ovarian cancer cells (SKOV3)...
February 4, 2017: Redox Biology
https://www.readbyqxmd.com/read/28235485/modulation-of-autophagy-in-exjsrv-env-transfected-cells-through-the-akt-mtor-and-mapk-signaling-pathway
#10
Xiaolin Sun, Fangyuan Du, Shuying Liu
The envelope (Env) of Jaagsiekte sheep retrovirus (JSRV) is an oncoprotein of ovine pulmonary adenocarcinoma (OPA). Autophagy is involved in different cancers, but how it is carcinogenic in JSRV Env is unclear. Modulation of autophagy in exJSRV-env-NM-transfected cells through the Akt/mTOR and MAPK signaling pathway was studied, and we observed strong positive labeling of p-Akt, p-mTOR, p-MEK1/2, p-ERK1/2, p-p38 and p-JNK in tumor cells and typical type II pneumocytes in naturally infected OPA lung tissues, which was co-aligned with JSRV-Env positive cells as shown by immunohistochemical and microscopic analysis...
February 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28230866/oridonin-induces-autophagy-via-inhibition-of-glucose-metabolism-in-p53-mutated-colorectal-cancer-cells
#11
Zhuo Yao, Fuhua Xie, Min Li, Zirui Liang, Wenli Xu, Jianhua Yang, Chang Liu, Hongwangwang Li, Hui Zhou, Liang-Hu Qu
The Warburg effect is an important characteristic of tumor cells, making it an attractive therapeutic target. Current anticancer drug development strategies predominantly focus on inhibitors of the specific molecular effectors involved in tumor cell proliferation. These drugs or natural compounds, many of which target the Warburg effect and the underlying mechanisms, still need to be characterized. To elucidate the anticancer effects of a natural diterpenoid, oridonin, we first demonstrated the anticancer activity of oridonin both in vitro and in vivo in colorectal cancer (CRC) cells...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28225086/uvrag-deficiency-exacerbates-doxorubicin-induced-cardiotoxicity
#12
Lin An, Xiao-Wen Hu, Shasha Zhang, Xiaowen Hu, Zongpei Song, Amber Naz, Zhenguo Zi, Jian Wu, Can Li, Yunzeng Zou, Lin He, Hongxin Zhu
Doxorubicin (DOX) is an effective chemotherapeutic drug in the treatment of various types of cancers. However, its clinical application has been largely limited by potential development of cardiotoxicity. Previously we have shown that ultra-violet radiation resistance-associated gene (UVRAG), an autophagy-related protein, is essential for the maintenance of autophagic flux in the heart under physiological conditions. Here, we sought to determine the role of UVRAG-mediated autophagy in DOX-induced cardiotoxicity...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28224423/prognostic-significance-of-autophagy-related-proteins-expression-in-resected-human-gastric-adenocarcinoma
#13
Bing Qu, Lei Yao, Hua-Ling Ma, Hong-Lei Chen, Zhi Zhang, Jiang Xie
Gastric adenocarcinoma (GC) is one of the most common malignancies in the world and one of the most frequent causes of cancer-related death. Autophagy is a highly regulated catabolic pathway responsible for the degradation of long-lived proteins and damaged intracellular organelles. However, the mechanism and guiding significance of autophagy in the development and progression of GC have remained to be elucidated. This study aimed to explore the clinicopathological significances and prognostic values of autophagy-related proteins AMBRA1 and Beclin-1 in GC...
February 2017: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/28223119/neferine-augments-therapeutic-efficacy-of-cisplatin-through-ros-mediated-non-canonical-autophagy-in-human-lung-adenocarcinoma-a549%C3%A2-cells
#14
Sivalingam Kalai Selvi, Amirthalingam Vinoth, Thiyagarajan Varadharajan, Ching Feng Weng, Viswanadha Vijaya Padma
Combination of dietary components with chemotherapy drugs is an emerging new strategy for cancer therapy to increase antitumor responses. Neferine, major bisbenzylisoquinoline alkaloid isolated from the seed embryo of Nelumbo nucifera (Lotus). In the present study, we investigated the efficacy of the combinatorial regimen of neferine and cisplatin compared to cisplatin high dose in human lung adenocarcinoma (A549) cells. Co-treatment with neferine enhanced cisplatin-induced autophagy in A549 cells was accompanied by Acidic vesicular accumulation (AVO), enhanced generation of reactive oxygen species (ROS) and depletion of intracellular glutathione (GSH), down regulation of PI3K/AKT/mTOR pathway, conversion of LC3B-I to LC3B-II...
February 18, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28222492/discovery-of-mieap-regulated-mitochondrial-quality-control-as-a-new-function-of-tumor-suppressor-p53
#15
REVIEW
Yasuyuki Nakamura, Hirofumi Arakawa
The tumor suppressor p53 gene is frequently mutated in human cancers, and the p53 protein suppresses cancer. However, the mechanism behind the p53-mediated tumor suppression is still unclear. Recently, Mieap (the mitochondria-eating protein) was identified as a p53-inducible protein. Mieap induces the accumulation of lysosomal proteins within mitochondria (MALM: Mieap-induced accumulation of lysosome-like organelles within mitochondria) in response to mitochondrial damage, and eliminates the oxidized mitochondrial proteins to repair unhealthy mitochondria...
February 21, 2017: Cancer Science
https://www.readbyqxmd.com/read/28219700/inhibition-of-ros-production-autophagy-or-apoptosis-signaling-reversed-the-anticancer-properties-of-antrodia-salmonea-in-triple-negative-breast-cancer-mda-mb-231-cells
#16
Chia-Ting Chang, Mallikarjuna Korivi, Hui-Chi Huang, Varadharajan Thiyagarajan, Kai-Yuan Lin, Pei-Jane Huang, Jer-Yuh Liu, You-Cheng Hseu, Hsin-Ling Yang
We investigated the in vitro and in vivo anticancer properties of Antrodia salmonea (AS), a well-known edible/medicinal mushroom in Taiwan, on human triple-negative breast cancer (MDA-MB-231) cells and xenografted nude mice; and revealed the underlying molecular mechanisms involved in autophagic- and apoptotic-cell death. Treatment of MDA-MB-231 cells with fermented culture broth of AS (0-200 μg/mL) inhibited cell viability/growth. AS-induced autophagy was evidenced via increased LC3-II accumulation, GFP-LC3 puncta and AVOs formation in MDA-MB-231 cells...
February 17, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28218691/zosteropenillines-%C3%A2-polyketides%C3%A2-from%C3%A2-the%C3%A2-marinederived%C3%A2-fungus%C3%A2-penicillium%C3%A2-thomii
#17
Shamil Sh Afiyatullov, Elena V Leshchenko, Dmitrii V Berdyshev, Maria P Sobolevskaya, Alexandr S Antonov, Vladimir A Denisenko, Roman S Popov, Mikhail V Pivkin, Anatoly A Udovenko, Evgeny A Pislyagin, Gunhild von Amsberg, Sergey A Dyshlovoy
Twelve new polyketides, zosteropenillines A-L (1-12), together with known polyketide pallidopenilline A (13), were isolated from the ethylacetate extract of the fungus Penicillium thomii associated with the seagrass Zostera marina. Their structures were established based on spectroscopic methods. The absolute configuration of zosteropenilline A (1) as 4R, 5S, 8S, 9R, 10R, and 13S was determined by a combination of the modified Mosher's method, X-ray analysis, and NOESY data. Absolute configurations of zosteropenillines B-D (2-4) were determined by timedependent density functional theory (TD-DFT) calculations of ECD spectra...
February 17, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28216370/targeting-autophagy-in-cancer-stem-cells-as-an-anticancer-therapy
#18
Yuanyuan Lei, Dan Zhang, Jin Yu, Hui Dong, Jianwei Zhang, Shiming Yang
Cancer stem cells (CSCs), which comprise a small proportion of total cancer cells, have special capacities for self-renewal, differentiation and tumor formation. Currently, CSCs are regarded as the major cause of the failure in anticancer therapy, such as chemoresistance and/or radioresistance, tumor recurrence and metastasis. Autophagy, a process of cellular self-digestion and response to stress, has a role in tumor formation and progression, and it may play a dual role in CSCs-related resistance to anticancer therapy...
February 17, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28216154/the-effect-of-indatraline-on-angiogenesis-suppression-through-hif-1%C3%AE-mediated-vegf-inhibition
#19
Chih-Na Yen, Yoon Sun Cho, Ho Jeong Kwon
The present research reports a novel biological activity of indatraline, a compound clinically used as an antidepressant. We previously identified indatraline as an autophagy inducer. Autophagy is an intracellular catabolic pathway for degrading or recycling unnecessary organelles in response to cellular stress. Indatraline-mediated autophagy induction results from mTOR inhibition. The mTOR is a negative regulator of autophagy as well as a master regulator of angiogenesis. Angiogenesis defines the process by which new vessels are formed from pre-existing vascular tissues, providing nutrients to cancer cells, allowing rapid tumor progression...
February 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28215799/comprehensive-understanding-of-pm2-5-on-gene-and-microrna-expression-patterns-in-zebrafish-danio-rerio-model
#20
Junchao Duan, Yang Yu, Yang Li, Li Jing, Man Yang, Ji Wang, Yanbo Li, Xianqing Zhou, Mark R Miller, Zhiwei Sun
PM2.5 is a major public health concern and some severe diseases have been attributed to exposure to PM2.5. However, a comprehensive understanding of gene and microRNA expression patterns induced by PM2.5 is missing. The objective of this study was to evaluate the toxicity of PM2.5 via genome-wide transcriptional analysis in the model teleost fish, zebrafish (Danio rerio). Gene ontology analysis revealed that the most impact gene functional categories induced by PM2.5 included oxidation-reduction process, transport, response to xenobiotic stimulus, response to chemical stimulus and metabolic process...
February 16, 2017: Science of the Total Environment
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