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Autophagy and cancer

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https://www.readbyqxmd.com/read/29244256/myricetin-induces-protective-autophagy-by-inhibiting-the-phosphorylation-of-mtor-in-hepg2-cells
#1
Jianping Cao, Hanwen Chen, Wei Lu, Yihua Wu, Xia Wu, Dajing Xia, Jiang Zhu
Myricetin, a natural flavonoid present in a variety of fruits and vegetables, has been studied as a promising cancer chemopreventive agent in many cancer models. It has been reported that myricetin could inhibit tumor promotion by inducing cell cycle arrest and promoting apoptotic cell death. At present, autophagy is considered to be closely associated with cancer, functioning as either an anti-cancer or pro-cancer mechanism depending on the cancer stage. Till date, the role of myricetin in regulating autophagy has not been reported...
December 15, 2017: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/29242405/digitalis-like-compounds-restore-hnis-expression-and-iodide-uptake-capacity-in-anaplastic-thyroid-cancer
#2
Marika H Tesselaar, Thomas Crezee, Imke Schuurmans, Danny Gerrits, James Nagarajah, Otto C Boerman, Ilse van Engen-van Grunsven, Johannes W A Smit, Romana T Netea-Maier, Theo S Plantinga
Purpose: Anaplastic thyroid cancer (ATC) is a rare malignancy that accounts for 1-2% of all thyroid cancers. ATC is one of the most aggressive human cancers, with rapid growth, tumor invasion and development of distant metastases. The median survival is only 5 months and the 1-year survival is less than 20%. Moreover, as a result of severe dedifferentiation including the loss of human sodium iodide symporter (hNIS) expression, radioactive iodide (RAI) therapy is ineffective. Recently, we have demonstrated beneficial effects of autophagy activating digitalis-like compounds (DLCs) on redifferentiation and concomitant restoration of iodide uptake in RAI-refractory papillary and follicular thyroid cancer cell lines...
December 14, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29241738/expression-of-autophagy-related-markers-at-the-surgical-margin-of-oral-squamous-cell-carcinoma-correlates-with-poor-prognosis-and-tumor-recurrence
#3
Takehito Terabe, Fumihiko Uchida, Hiroki Nagai, Shoei Omori, Naomi Ishibashi-Kanno, Shogo Hasegawa, Kenji Yamagata, Masahiko Gosho, Toru Yanagawa, Hiroki Bukawa
Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide, and is associated with poor prognosis. Autophagy is a programmed cell survival mechanism involved in physiologic processes and various diseases including cancer. However, the relationship between autophagy and cancer is controversial. Several studies have claimed that the expression of autophagy-related proteins, namely microtubule-associated protein light chain3 (LC3) and p62/SQSTM1 (p62), is associated with poor prognosis in OSCC...
December 11, 2017: Human Pathology
https://www.readbyqxmd.com/read/29241092/trehalose-protects-against-oxidative-stress-by-regulating-the-keap1-nrf2-and-autophagy-pathways
#4
Yuhei Mizunoe, Masaki Kobayashi, Yuka Sudo, Shukoh Watanabe, Hiromine Yasukawa, Daiki Natori, Ayana Hoshino, Arisa Negishi, Naoyuki Okita, Masaaki Komatsu, Yoshikazu Higami
Dysfunction of autophagy, which regulates cellular homeostasis by degrading organelles and proteins, is associated with pathogenesis of various diseases such as cancer, neurodegeneration and metabolic disease. Trehalose, a naturally occurring nontoxic disaccharide found in plants, insects, microorganisms and invertebrates, but not in mammals, was reported to function as a mechanistic target of the rapamycin (mTOR)-independent inducer of autophagy. In addition, trehalose functions as an antioxidant though its underlying molecular mechanisms remain unclear...
September 20, 2017: Redox Biology
https://www.readbyqxmd.com/read/29240697/cymantrenyl-nucleobases-synthesis-anticancer-antitrypanosomal-and-antimicrobial-activity-studies
#5
Artur Jabłoński, Karolina Matczak, Aneta Koceva-Chyła, Kamil Durka, Dietmar Steverding, Katarzyna Jakubiec-Krześniak, Jolanta Solecka, Damian Trzybiński, Krzysztof Woźniak, Vanesa Andreu, Gracia Mendoza, Manuel Arruebo, Krzysztof Kochel, Barbara Krawczyk, Dominik Szczukocki, Konrad Kowalski
The synthesis of four cymantrene-5-fluorouracil derivatives (1-4) and two cymantrene-adenine derivatives (5 and 6) is reported. All of the compounds were characterized by spectroscopic methods and the crystal structure of two derivatives (1 and 6), together with the previously described cymantrene-adenine compound C was determined by X-ray crystallography. While the compounds 1 and 6 crystallized in the triclinic P-1 space group, compound C crystallized in the monoclinic P2₁/m space group. The newly synthesized compounds 1-6 were tested together with the two previously described cymantrene derivatives B and C for their in vitro antiproliferative activity against seven cancer cell lines (MCF-7, MCF-7/DX, MDA-MB-231, SKOV-3, A549, HepG2m and U-87-MG), five bacterial strains Staphylococcus aureus (methicillin-sensitive, methicillin-resistant and vancomycin-intermediate strains), Staphylococcus epidermidis, and Escherichia coli, including clinical isolates of S...
December 14, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29240252/ganoderma-microsporum-immunomodulatory-protein-induces-apoptosis-and-potentiates-mitomycin-c-induced-apoptosis-in-urinary-bladder-urothelial-carcinoma-cells
#6
Sheng-Yuan Huang, Chih-Cheng Chien, Ruey-Shyang Hseu, Victoria Ying Jen Huang, Shang Ying Chiang, Chi-Jung Huang, Shao-Kuan Chen, Ru-Yin Tsai, Hsi-Ting Lin, Yu-Che Cheng
Current chemotherapy and immunotherapy treatments followed by transurethral resection for urinary bladder urothelial carcinoma (UC) usually suffers from poor prognosis and high recurrence rate. Design and modification of current formulation with the novel adjuvants is needed. A recombinant protein derived from Ganoderma microsporum named as Ganoderma microsporum immunomodulatory protein (GMIP) were used to treat UC cells. We found GMIP elicits a dose-dependent and time-dependent anti-UC cell proliferation effect, with a half-maximal inhibition concentration (IC50 ) comparable to mitomycin C (MMC), a commonly used chemotherapy agent...
December 14, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29240246/hyperthermia-enhances-radiosensitivity-of-colorectal-cancer-cells-through-ros-inducing-autophagic-cell-death
#7
Ming-Chen Ba, Hui Long, Shuai Wang, Yin-Bing Wu, Bo-Huo Zhang, Zhao-Fei Yan, Fei-Hong Yu, Shu-Zhong Cui
BACKGROUND: Hyperthermia (HT) enhances the anti-cancer effects of radiotherapy (RT), but the precise biochemical mechanisms involved are unclear. This study was aim to investigate if mild HT sensitizes colorectal cancer cells to RT through reactive oxygen species (ROS)-inducing autophagic cell death in a mice model of HCT116 human colorectal cancer. METHODS: HCT116 mice model were randomly divided into five groups: mock group, hyperthermia group (HT), radiotherapy group (RT), HT + RT group, and HT + RT +N-acetyl L-cysteine (NAC) group (HT + CT + NAC)...
December 14, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29239350/suppression-of-eef-2k-mediated-autophagy-enhances-the-cytotoxicity-of-raddeanin-a-against-human-breast-cancer-cells-in-vitro
#8
Yi-di Guan, Shi-Long Jiang, Pian Yu, Mei Wen, Yi Zhang, Song-Shu Xiao, Xiao-Jun Xu, Yan Cheng
Recent evidence shows that raddeanin A (RA), an oleanane-type triterpenoid saponin extracted from Anemone raddeana Regel, exerts remarkable cytotoxicity against cancer cells in vitro and in vivo. In addition, RA has also been found to activate autophagy in human gastric cancer cells. In this study, we investigated the molecular mechanisms underlying RA-induced autophagy as well as the relationship between RA-induced autophagy and its cytotoxicity in human breast cancer cells in vitro. Treatment with RA (2-8 μmol/L) dose-dependently enhanced autophagy, as evidenced by increased LC3 levels in breast cancer cell lines T47D, MCF-7 and MDA-MB-231...
December 14, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29238973/demethylzeylasteral-zst93-inhibits-cell-growth-and-enhances-cell-chemosensitivity-to-gemcitabine-in-human-pancreatic-cancer-cells-via-apoptotic-and-autophagic-pathways
#9
Feng Wang, Xiaodong Tian, Zhengkui Zhang, Yongsu Ma, Xuehai Xie, Jian Liang, Chunxin Yang, Yinmo Yang
The overall 5-year survival rate of patients with human pancreatic cancer remains less than 8% because of its aggressive growth, early metastasis, and resistance to conventional chemoradiotherapy. It is essential to develop innovative and effective therapeutic agents to improve its prognosis. Demethylzeylasteral (ZST93) is a novel triterpenoid monomer extracted from the xylem of Tripterygium roots. This study aimed to assess the effects of ZST93 on cell proliferation and its role in the chemosensitivity to gemcitabine in human pancreatic cancer cells...
December 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29238039/helicobacter-pylori-vaca-induces-autophagic-cell-death-in-gastric-epithelial-cells-via-the-endoplasmic-reticulum-stress-pathway
#10
Pan Zhu, Jun Xue, Zhu-Jun Zhang, Yin-Ping Jia, Ya-Nan Tong, Dan Han, Qian Li, Yang Xiang, Xu-Hu Mao, Bin Tang
The Helicobacter pylori vacuolating cytotoxin (VacA) can promote progressive vacuolation and gastric injury and may be associated with human gastric cancer. Increasing evidence indicates that autophagy is involved in the cell death induced by VacA, but the specific mechanisms need to be further elucidated. We show here that VacA could induce autophagy and increase cell death in human gastric cancer cell lines. Further investigations revealed that inhibition of autophagy could decrease the VacA-induced cell death in AGS cells...
December 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29237720/beyond-self-eating-the-control-of-nonautophagic-functions-and-signaling-pathways-by-autophagy-related-proteins
#11
REVIEW
Ken Cadwell, Jayanta Debnath
The identification of conserved autophagy-related proteins (ATGs) that mediate bulk degradation of cytosolic material laid the foundation for breakthroughs linking autophagy to a litany of physiological processes and disease conditions. Recent discoveries are revealing that these same ATGs orchestrate processes that are related to, and yet clearly distinct from, classic autophagy. Autophagy-related functions include secretion, trafficking of phagocytosed material, replication and egress of viral particles, and regulation of inflammatory and immune signaling cascades...
December 13, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29235250/discovery-and-mechanistic-elucidation-of-a-class-of-pdi-inhibitors-for-the-treatment-of-glioblastoma
#12
Anahita Kyani, Shuzo Tamura, Suhui Yang, Andrea Shergalis, Soma Somanta, Yuting Kuang, Mats Ljungman, Nouri Neamati
Protein disulfide isomerase (PDI) is overexpressed in glioblastoma, the most aggressive form of brain cancer, and folds nascent proteins responsible for the progression and spread of the disease. Herein, we describe a novel, nanomolar PDI inhibitor, pyrimidotriazinedione 35G8, that is toxic in a panel of human glioblastoma cell lines. We performed a medium throughput 20,000-compound screen of a diverse subset of 1,000,000 compounds to identify cytotoxic small molecules. Cytotoxic compounds were screened for PDI inhibition, and, from the screen, 35G8 emerged as the most cytotoxic inhibitor of PDI...
December 12, 2017: ChemMedChem
https://www.readbyqxmd.com/read/29234488/sirt6-histone-deacetylase-functions-as-a-potential-oncogene-in-human-melanoma
#13
Liz Mariely Garcia-Peterson, Mary Ann Ndiaye, Chandra K Singh, Gagan Chhabra, Wei Huang, Nihal Ahmad
Melanoma is an aggressive skin cancer that can rapidly metastasize to become fatal, if not diagnosed early. Despite recent therapeutic advances, management of melanoma remains difficult. Therefore, novel molecular targets and strategies are required to manage this neoplasm. This study was undertaken to determine the role of the sirtuin SIRT6 in melanoma. Employing a panel of human melanoma cells and normal human melanocytes, we found significant SIRT6 mRNA and protein upregulation in melanoma cells. Further, using a tissue microarray coupled with quantitative Vectra analysis, we demonstrated significant SIRT6 overexpression in human melanoma tissues...
September 2017: Genes & Cancer
https://www.readbyqxmd.com/read/29234486/jnk-signaling-a-multiplexing-hub-in-programmed-cell-death
#14
REVIEW
Danny N Dhanasekaran, E Premkumar Reddy
Jun N-terminal kinases or JNKs have been shown to be involved in a wide array of signaling events underlying tumorigenesis and tumor progression. Through its interaction with a diverse set of signaling proteins and adaptors, JNKs regulate cell proliferation, invasive migration, therapy resistance, and programmed cell death. JNKs have been shown to play a role in apoptotic as well as non-apoptotic programmed cell death mechanisms including those of necroptosis, ferroptosis, pyroptosis, and autophagy. Most of the tumorigenic regulatory functions of JNKs can be related to their ability to module cell death via these programmed cell death mechanisms...
September 2017: Genes & Cancer
https://www.readbyqxmd.com/read/29233879/exploiting-cancer-vulnerabilities-mtor-autophagy-and-homeostatic-imbalance
#15
REVIEW
Charlotte E Johnson, Andrew R Tee
Mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) at lysosomes plays a pivotal role in cell growth control where an array of large multiprotein complexes relay nutrient, energy, and growth signal inputs through mTORC1. In cancer cells, such regulation often becomes disconnected, leading to uncontrolled cell growth and an elevation in cellular stress. Consequently, cancer cells often lose homeostatic balance as they grow in unfavorable conditions, i.e. when nutrients and energy are limited yet mTORC1 is still aberrantly activated...
December 12, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/29233876/molecular-control-of-chaperone-mediated-autophagy
#16
REVIEW
Steve Catarino, Paulo Pereira, Henrique Girão
Chaperone-mediated autophagy (CMA) is a selective form of autophagy in which cytosolic proteins bearing a pentapeptide motif biochemically related to the KFERQ sequence, are recognized by the heat shock protein family A member 8 (HSPA8) chaperone, delivered to the lysomal membrane, and directly translocated across the lysosomal membrane by a protein complex containing lysosomal associated membrane protein 2a (Lamp2a). Since its discovery over two decades ago, the importance of this pathway in cell proteostasis has been made increasingly apparent...
December 12, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/29233875/to-be-or-not-to-be-cell-autonomous-autophagy-says-both
#17
REVIEW
Nina Fenouille, Anna Chiara Nascimbeni, Joëlle Botti-Millet, Nicolas Dupont, Etienne Morel, Patrice Codogno
Although cells are a part of the whole organism, classical dogma emphasizes that individual cells function autonomously. Many physiological and pathological conditions, including cancer, and metabolic and neurodegenerative diseases, have been considered mechanistically as cell-autonomous pathologies, meaning those that damage or defect within a selective population of affected cells suffice to produce disease. It is becoming clear, however, that cells and cellular processes cannot be considered in isolation...
December 12, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/29233869/mtorc1-as-the-main-gateway-to-autophagy
#18
REVIEW
Yoana Rabanal-Ruiz, Elsje G Otten, Viktor I Korolchuk
Cells and organisms must coordinate their metabolic activity with changes in their environment to ensure their growth only when conditions are favourable. In order to maintain cellular homoeostasis, a tight regulation between the synthesis and degradation of cellular components is essential. At the epicentre of the cellular nutrient sensing is the mechanistic target of rapamycin complex 1 (mTORC1) which connects environmental cues, including nutrient and growth factor availability as well as stress, to metabolic processes in order to preserve cellular homoeostasis...
December 12, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/29232549/stressing-out-panin-nrf2-pushes-over-the-edge
#19
Laura Torrente, Gina M DeNicola
The mechanisms by which chronic stress promote the development of pancreatic ductal adenocarcinoma (PDAC) are poorly defined. In this issue of Cancer Cell, Todoric et al. discover a role for impaired autophagy in the development of PDAC through p62-mediated activation of NRF2.
December 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29231261/lncrna-awpph-inhibits-smad4-via-ezh2-to-regulate-bladder-cancer-progression
#20
Feng Zhu, Xinjun Zhang, Qinnan Yu, Guangye Han, Fengxia Diao, Chunlei Wu, Yan Zhang
This study aimed to investigate the effect and underlying mechanism of lncRNA AWPPH in bladder cancer (BC). Totally, 20 Ta-T1 stage BC tissues, 20 T2-T4 stage BC tissues and 20 normal bladder tissues, as well as human bladder epithelial cell line SV-HUC-1, human BC cell lines RT4 and T24 were obtained to detect the levels of AWPPH, enhancer of zeste homolog 2 (EZH2), and SMAD4 using RT-qPCR or western blotting. RT4 cells were transfected with pc-AWPPH, pc-EZH2 or pc-control, and T24 cells were transfected with si-AWPPH, si-EZH2, si-control, or pc-AWPPH + pc-SMAD4, respectively...
December 12, 2017: Journal of Cellular Biochemistry
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