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Senescence, cancer, autophagy

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https://www.readbyqxmd.com/read/29435183/expression-and-function-of-nuclear-receptor-coactivator-4-isoforms-in-transformed-endometriotic-and-malignant-ovarian-cells
#1
Stephanie Rockfield, Idhaliz Flores, Meera Nanjundan
Iron is proposed to contribute to the transition from endometriosis to specific subtypes of ovarian cancers (OVCAs). Regulation of intracellular iron occurs via a ferritinophagic process involving NCOA4 (Nuclear Receptor Coactivator 4), represented by two major isoforms (NCOA4α and NCOA4β), whose contribution to ovarian cancer biology remains uninvestigated. We thus generated transformed endometriotic cells (via HRAS V12A , c-MYC T58A , and p53 inactivation) whose migratory potential was increased in response to conditioned media from senescent endometriotic cells...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29435080/a-novel-approach-to-glioma-therapy-using-an-oncolytic-adenovirus-with-two-specific-promoters
#2
Feng Liu, Kaya Xu, Hua Yang, Yuming Li, Jian Liu, Jixiang Wang, Zhizhong Guan
Gliomas are the most common type of primary brain tumor in adults, where more than half of the cases are malignant, and the prognosis is poor. The early viral 1A (E1A) protein has been widely recognized to be essential for adenoviral replication and production of progeny virions in human cells, a process that is regulated by human telomerase reverse transcriptase. The p53 gene, as a tumor suppressor, regulates diverse cellular processes, including cell cycle arrest, cell autophagy, senescence and apoptosis...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29405784/carvacrol-nanoemulsion-evokes-cell-cycle-arrest-apoptosis-induction-and-autophagy-inhibition-in-doxorubicin-resistant-a549-cell-line
#3
Imran Khan, Ashutosh Bahuguna, Monika Bhardwaj, Tejinder Pal Khaket, Sun Chul Kang
Carvacrol is a monoterpenoid flavonoid found abundantly in thyme plants. Its physiochemical instability and partial solubility in water is the principal limitation for its industrial use. Hence, we made a carvacrol nanoemulsion (CANE) using ultrasonication method and characterized it by dynamic light scattering (DLS) technique which revealed a negative surface charge (-29.89 mV) with 99.1 nm average droplet size. CANE effectively induced apoptosis in doxorubicin-resistant A549 lung carcinoma cells (A549 DR ) evident by the elevated expression of apoptotic proteins such as Bax, Cytochrome C, and Cleaved caspase 3 and 9...
February 6, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29371440/spermidine-in-health-and-disease
#4
REVIEW
Frank Madeo, Tobias Eisenberg, Federico Pietrocola, Guido Kroemer
Interventions that delay aging and protect from age-associated disease are slowly approaching clinical implementation. Such interventions include caloric restriction mimetics, which are defined as agents that mimic the beneficial effects of dietary restriction while limiting its detrimental effects. One such agent, the natural polyamine spermidine, has prominent cardioprotective and neuroprotective effects and stimulates anticancer immunosurveillance in rodent models. Moreover, dietary polyamine uptake correlates with reduced cardiovascular and cancer-related mortality in human epidemiological studies...
January 26, 2018: Science
https://www.readbyqxmd.com/read/29331584/protein-neddylation-and-its-alterations-in-human-cancers-for-targeted-therapy
#5
REVIEW
Lisha Zhou, Wenjuan Zhang, Yi Sun, Lijun Jia
Neddylation, a post-translational modification that conjugates an ubiquitin-like protein NEDD8 to substrate proteins, is an important biochemical process that regulates protein function. The best-characterized substrates of neddylation are the cullin subunits of Cullin-RING ligases (CRLs), which, as the largest family of E3 ubiquitin ligases, control many important biological processes, including tumorigenesis, through promoting ubiquitylation and subsequent degradation of a variety of key regulatory proteins...
January 10, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29320480/pharmacological-activation-of-rev-erbs-is-lethal-in-cancer-and-oncogene-induced-senescence
#6
Gabriele Sulli, Amy Rommel, Xiaojie Wang, Matthew J Kolar, Francesca Puca, Alan Saghatelian, Maksim V Plikus, Inder M Verma, Satchidananda Panda
The circadian clock imposes daily rhythms in cell proliferation, metabolism, inflammation and DNA damage response. Perturbations of these processes are hallmarks of cancer and chronic circadian rhythm disruption predisposes individuals to tumour development. This raises the hypothesis that pharmacological modulation of the circadian machinery may be an effective therapeutic strategy for combating cancer. REV-ERBs, the nuclear hormone receptors REV-ERBα (also known as NR1D1) and REV-ERBβ (also known as NR1D2), are essential components of the circadian clock...
January 18, 2018: Nature
https://www.readbyqxmd.com/read/29234488/sirt6-histone-deacetylase-functions-as-a-potential-oncogene-in-human-melanoma
#7
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/29180229/peroxisomes-contribute-to-oxidative-stress-in-neurons-during-doxorubicin-based-chemotherapy
#8
Jose F Moruno-Manchon, Ndidi-Ese Uzor, Shelli R Kesler, Jeffrey S Wefel, Debra M Townley, Archana Sidalaghatta Nagaraja, Sunila Pradeep, Lingegowda S Mangala, Anil K Sood, Andrey S Tsvetkov
Doxorubicin, a commonly used anti-neoplastic agent, causes severe neurotoxicity. Doxorubicin promotes thinning of the brain cortex and accelerates brain aging, leading to cognitive impairment. Oxidative stress induced by doxorubicin contributes to cellular damage. In addition to mitochondria, peroxisomes also generate reactive oxygen species (ROS) and promote cell senescence. Here, we investigated if doxorubicin affects peroxisomal homeostasis in neurons. We demonstrate that the number of peroxisomes is increased in doxorubicin-treated neurons and in the brains of mice which underwent doxorubicin-based chemotherapy...
January 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29167573/metformin-transiently-inhibits-colorectal-cancer-cell-proliferation-as-a-result-of-either-ampk-activation-or-increased-ros-production
#9
Angela Mogavero, Maria Valeria Maiorana, Susanna Zanutto, Luca Varinelli, Fabio Bozzi, Antonino Belfiore, Chiara C Volpi, Annunziata Gloghini, Marco A Pierotti, Manuela Gariboldi
Metformin is a widely used and well-tolerated anti-diabetic drug that can reduce cancer risk and improve the prognosis of certain malignancies. However, the mechanism underlying its anti-cancer effect is still unclear. We studied the anti-cancer activity of metformin on colorectal cancer (CRC) by using the drug to treat HT29, HCT116 and HCT116 p53-/- CRC cells. Metformin reduced cell proliferation and migration by inducing cell cycle arrest in the G0/G1 phase. This was accompanied by a sharp decrease in the expression of c-Myc and down-regulation of IGF1R...
November 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29165552/what-happened-to-the-igf-binding-proteins
#10
Leon A Bach
Insulin-like growth factor binding proteins (IGFBPs) 1-6 are high affinity regulators of IGF activity. They generally inhibit IGF actions by preventing binding to the IGF-I receptor but may also enhance their actions under some conditions. Post-translational modifications such as glycosylation and phosphorylation modulate IGFBP properties, and IGFBP proteolysis results in IGF release. IGFBPs have more recently been shown to have IGF-independent actions. A number of mechanisms are involved, including modulation of other growth factor pathways, nuclear localization and transcriptional regulation, interaction with the sphingolipid pathway, and binding to non-IGF biomolecules in the extracellular space and matrix, on the cell surface and intracellularly...
November 20, 2017: Endocrinology
https://www.readbyqxmd.com/read/29147906/regulation-of-signal-transduction-by-dj-1
#11
Stephanie E Oh, M Maral Mouradian
The ability of DJ-1 to modulate signal transduction has significant effects on how the cell regulates normal processes such as growth, senescence, apoptosis, and autophagy to adapt to changing environmental stimuli and stresses. Perturbations of DJ-1 levels or function can disrupt the equilibrium of homeostatic signaling networks and set off cascades that play a role in the pathogenesis of conditions such as cancer and Parkinson's disease.DJ-1 plays a major role in various pathways. It mediates cell survival and proliferation by activating the extracellular signal-regulated kinase (ERK1/2) pathway and the phosphatidylinositol-3-kinase (PI3K)/Akt pathway...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29137236/the-nucleocytoplasmic-translocation-and-up-regulation-of-ing5-protein-in-breast-cancer-a-potential-target-for-gene-therapy
#12
Xiao-Qing Ding, Shuang Zhao, Lei Yang, Xin Zhao, Gui-Feng Zhao, Shu-Peng Zhao, Zhi-Jie Li, Hua-Chuan Zheng
Here, we found that ING5 overexpression resulted in a lower proliferation, reduced glucose metabolism, S arrest, decreased migration and invasion, apoptotic induction, fat accumulation, autophagy, senescence and mesenchymal-epithelial-transition of breast cancer cells. It also suppressed the tumor growth of breast cancer cells by inhibiting proliferation, inducing apoptosis and autophagy. ING5-mediated chemoresistance was positively linked to Akt and NF-κB activation, MRP1 and GST-π overexpression, and FBXW7 hypoexpression...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29130426/nupr1-maintains-autolysosomal-efflux-by-activating-snap25-transcription-in-cancer-cells
#13
Yanchao Mu, Xiaojie Yan, Ding Li, Dan Zhao, Lingling Wang, Xiaoyang Wang, Dan Gao, Jie Yang, Hua Zhang, Yanzhe Li, Yanan Sun, Yiliang Wei, Zhenfa Zhang, Xinzhong Chang, Zhi Yao, Shanshan Tian, Kai Zhang, Lance S Terada, Zhenyi Ma, Zhe Liu
In the advanced stages of cancer, autophagy is thought to promote tumor progression through its ability to mitigate various cellular stresses. However, the details of how autophagy is homeostatically regulated in such tumors are unknown. Here, we report that NUPR1 (nuclear protein 1, transcriptional regulator), a transcriptional coregulator, is aberrantly expressed in a subset of cancer cells and predicts low overall survival rates for lung cancer patients. NUPR1 regulates the late stages of autolysosome processing through the induction of the SNARE protein SNAP25, which forms a complex with the lysosomal SNARE-associated protein VAMP8...
November 13, 2017: Autophagy
https://www.readbyqxmd.com/read/29104175/autophagic-cell-death-and-premature-senescence-new-mechanism-of-5-fluorouracil-and-sulforaphane-synergistic-anticancer-effect-in-mda-mb-231-triple-negative-breast-cancer-cell-line
#14
Małgorzata Milczarek, Katarzyna Wiktorska, Lidia Mielczarek, Mirosława Koronkiewicz, Aleksandra Dąbrowska, Katarzyna Lubelska, Dariusz Matosiuk, Zdzisław Chilmonczyk
In view of the need for new, more effective therapies for the triple negative breast cancer treatment, the aim of the study was to evaluate the anticancer activity and mechanism of action of the sulforaphane and 5-fluorouracil combination in the triple negative breast cancer cell line MDA-MB-231. Changes in the number of live cells after alone and sequential treatment were determined by the MTT test. The Chou and Talaly method was used to identify the type of interaction. Confocal microscopy, flow cytometry, western blot and spectrophotometry were used to examine apoptosis, autophagy and premature senescence...
November 2, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28993779/natural-killer-cell-response-to-chemotherapy-stressed-cancer-cells-role-in-tumor-immunosurveillance
#15
REVIEW
Alessandra Zingoni, Cinzia Fionda, Cristiana Borrelli, Marco Cippitelli, Angela Santoni, Alessandra Soriani
Natural killer (NK) cells are innate cytotoxic lymphoid cells that actively prevent neoplastic development, growth, and metastatic dissemination in a process called cancer immunosurveillance. An equilibrium between immune control and tumor growth is maintained as long as cancer cells evade immunosurveillance. Therapies designed to kill cancer cells and to simultaneously sustain host antitumor immunity are an appealing strategy to control tumor growth. Several chemotherapeutic agents, depending on which drugs and doses are used, give rise to DNA damage and cancer cell death by means of apoptosis, immunogenic cell death, or other forms of non-apoptotic death (i...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28990419/proline-metabolism-in-cell-regulation-and-cancer-biology-recent-advances-and-hypotheses
#16
James M Phang
SIGNIFICANCE: It is increasingly clear that proline metabolism plays an important role in metabolic reprogramming, not only in cancer but also in related fields such as aging, senescence, and development. Although first focused on proline catabolism, recent studies from a number of laboratories have emphasized the regulatory effects of proline synthesis and proline cycling. Recent Advances: Although proline dehydrogenase/proline oxidase (PRODH/POX) has been known as a tumor protein 53 (P53)-activated source of redox signaling for initiating apoptosis and autophagy, senescence has been added to the responses...
November 15, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28989041/deciphering-molecular-mechanisms-of-arginine-deiminase-based-therapy-comparative-response-analysis-in-paired-human-primary-and-recurrent-glioblastomas
#17
Claudia Maletzki, Yvonne Rosche, Christin Riess, Aline Scholz, Doreen William, Carl Friedrich Classen, Bernd Kreikemeyer, Michael Linnebacher, Tomas Fiedler
Arginine auxotrophy constitutes the Achilles' heel for several tumors, among them glioblastoma multiforme (GBM). Hence, arginine-depleting enzymes such as arginine deiminase (ADI) from Streptococcus pyogenes are promising for treatment of primary and maybe even refractory GBM. Based on our previous study in which ADI-susceptibility was shown on a panel of patient-derived GBM cell lines, we here aimed at deciphering underlying molecular mechanisms of ADI-mediated growth inhibition. We found that ADI (35 mU/mL) initially induces a cellular stress-response that is characterized by upregulation of genes primarily belonging to the heat-shock protein family...
October 5, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28954246/cytoprotective-mechanisms-of-dj-1-against-oxidative-stress-through-modulating-erk1-2-and-ask1-signal-transduction
#18
REVIEW
Stephanie E Oh, M Maral Mouradian
DJ-1 is a highly conserved multifunctional protein linked to both neurodegeneration and neoplasia. Among its various activities is an antioxidant property leading to cytoprotection under oxidative stress conditions. This is associated with the ability to modulate signal transduction events that determine how the cell regulates normal processes such as growth, senescence, apoptosis, and autophagy in order to adapt to environmental stimuli and stresses. Alterations in DJ-1 expression or function can disrupt homeostatic signaling networks and initiate cascades that play a role in the pathogenesis of conditions such as Parkinson's disease and cancer...
September 18, 2017: Redox Biology
https://www.readbyqxmd.com/read/28947133/palbociclib-induced-autophagy-and-senescence-in-gastric-cancer-cells
#19
Claudio A Valenzuela, Leandro Vargas, Valentina Martinez, Sindy Bravo, Nelson E Brown
Targeting cyclin D-CDK4/6 kinase complexes has recently been shown to increase the survival of breast cancer patients with estrogen receptor positive breast tumors. Based on these outcomes, CDK4/6 inhibitors are currently being tested, alone o in combination with other drugs, in the treatment of other malignancies characterized by hyper-activation of cyclin D-CDK4/6 complexes. Nonetheless, a better understanding of the cellular processes that are implemented in response to CDK4/6 inhibition is necessary to expand the therapeutic window and confront the development of drug resistance...
November 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28923415/diindolylmethane-and-its-halogenated-derivatives-induce-protective-autophagy-in-human-prostate-cancer-cells-via-induction-of-the-oncogenic-protein-aeg-1-and-activation-of-amp-activated-protein-kinase-ampk
#20
Hossam Draz, Alexander A Goldberg, Vladimir I Titorenko, Emma S Tomlinson Guns, Stephen H Safe, J Thomas Sanderson
3,3'-Diindolylmethane (DIM) and its synthetic halogenated derivatives 4,4'-Br2- and 7,7'-Cl2DIM (ring-DIMs) have recently been shown to induce protective autophagy in human prostate cancer cells. The mechanisms by which DIM and ring-DIMs induce autophagy have not been elucidated. As DIM is a mitochondrial ATP-synthase inhibitor, we hypothesized that DIM and ring-DIMs induce autophagy via alteration of intracellular AMP/ATP ratios and activation of AMP-activated protein kinase (AMPK) signaling in prostate cancer cells...
December 2017: Cellular Signalling
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