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Senescence, cancer, autophagy

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https://www.readbyqxmd.com/read/29663364/impact-of-iaspp-on-chemoresistance-through-plk1-and-autophagy-in-ovarian-clear-cell-carcinoma
#1
Ka-Kui Chan, Oscar Gee-Wan Wong, Esther Shuk-Ying Wong, Karen Kar-Loen Chan, Philip Pun-Ching Ip, Ka-Yu Tse, Annie Nga-Yin Cheung
Ovarian clear cell carcinoma (OCCC) is a type of epithelial ovarian cancer that is strongly associated with endometriosis, resistance against conventional chemotherapy and thus poorer prognosis. The expression of inhibitory member of the ASPP family proteins (iASPP) and Polo-like kinase (PLK)1 were significantly higher in OCCC compared to benign cystadenomas and endometriosis. Both protein expressions were found to correlate with chemoresistance in patients with OCCC while high iASPP expression alone was significantly associated with a poor patient survival...
April 16, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29645088/impact-of-iaspp-on-chemoresistance-through-plk1-and-autophagy-in-ovarian-clear-cell-carcinoma
#2
Ka-Kui Chan, Oscar Gee-Wan Wong, Esther Shuk-Ying Wong, Karen Kar-Loen Chan, Philip Pun-Ching Ip, Ka-Yu Tse, Annie Nga-Yin Cheung
Ovarian clear cell carcinoma (OCCC) is a type of epithelial ovarian cancer that is strongly associated with endometriosis, resistance against conventional chemotherapy and thus poorer prognosis. The expression of inhibitory member of the ASPP family proteins (iASPP) and Polo-like kinase (PLK)1 were significantly higher in OCCC compared to benign cystadenomas and endometriosis. Both protein expressions were found to correlate with chemoresistance in patients with OCCC while high iASPP expression alone was significantly associated with a poor patient survival...
April 12, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29608137/mechanisms-and-functions-of-cellular-senescence
#3
Nicolás Herranz, Jesús Gil
Cellular senescence is a highly stable cell cycle arrest that is elicited in response to different stresses. By imposing a growth arrest, senescence limits the replication of old or damaged cells. Besides exiting the cell cycle, senescent cells undergo many other phenotypic alterations such as metabolic reprogramming, chromatin rearrangement, or autophagy modulation. In addition, senescent cells produce and secrete a complex combination of factors, collectively referred as the senescence-associated secretory phenotype, that mediate most of their non-cell-autonomous effects...
April 2, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29588413/hydrophobic-patches-on-smad2-and-smad3-determine-selective-binding-to-cofactors
#4
Ken-Ichi Miyazono, Saho Moriwaki, Tomoko Ito, Akira Kurisaki, Makoto Asashima, Masaru Tanokura
The transforming growth factor-β (TGF-β) superfamily of cytokines regulates various biological processes, including cell proliferation, immune responses, autophagy, and senescence. Dysregulation of TGF-β signaling causes various diseases, such as cancer and fibrosis. SMAD2 and SMAD3 are core transcription factors involved in TGF-β signaling, and they form heterotrimeric complexes with SMAD4 (SMAD2-SMAD2-SMAD4, SMAD3-SMAD3-SMAD4, and SMAD2-SMAD3-SMAD4) in response to TGF-β signaling. These heterotrimeric complexes interact with cofactors to control the expression of TGF-β-dependent genes...
March 27, 2018: Science Signaling
https://www.readbyqxmd.com/read/29579719/copper-accumulation-in-senescent-cells-interplay-between-copper-transporters-and-impaired-autophagy
#5
Shashank Masaldan, Sharnel A S Clatworthy, Cristina Gamell, Zoe M Smith, Paul S Francis, Delphine Denoyer, Peter M Meggyesy, Sharon La Fontaine, Michael A Cater
Cellular senescence is characterized by irreversible growth arrest incurred through either replicative exhaustion or by pro-oncogenic cellular stressors (radioactivity, oxidative stress, oncogenic activation). The enrichment of senescent cells in tissues with age has been associated with tissue dyshomeostasis and age-related pathologies including cancers, neurodegenerative disorders (e.g. Alzheimer's, Parkinson's, etc.) and metabolic disorders (e.g. diabetes). We identified copper accumulation as being a universal feature of senescent cells [mouse embryonic fibroblasts (MEF), human prostate epithelial cells and human diploid fibroblasts] in vitro...
March 17, 2018: Redox Biology
https://www.readbyqxmd.com/read/29574749/targeting-egfr-mediated-autophagy-as-a-potential-strategy-for-cancer-therapy
#6
REVIEW
Mopa Alina Sooro, Ni Zhang, Pinghu Zhang
Autophagy is a naturally-occurring programmed cellular catabolic process stimulated by cellular stress for energy homeostasis maintenance and elimination of harmful substances. It mostly works as pro-survival mechanism but on the other hand deregulation of autophagy has been linked to non-apoptotic cell death known as 'type II programmed cell death'. Emerging evidences indicate that EGFR (epidermal growth factor receptor)-mediated RAS-RAF-MEK-ERK signaling pathway plays a critical role in the induction of autophagy in various tumors...
March 25, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29574020/sirt1-and-micrornas-the-role-in-breast-lung-and-prostate-cancers
#7
REVIEW
Hedyieh Karbasforooshan, Ali Roohbakhsh, Gholamreza Karimi
Breast cancer and prostate cancer are the most common malignant tumors in female and men, respectively. Furthermore, lung cancer is the leading cause of cancer deaths worldwide. It is an emergency to develop a powerful strategy to treat these threatening cancers more effectively, because of low efficacy and high rates of chemotherapy effects. MicroRNAs (miRNAs), a class of small non-coding RNAs, are key regulators of gene expression via induction of translational repression or mRNA degradation. MiRNA deregulation has been linked to cancer initiation and progression...
March 21, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29562589/an-interplay-between-senescence-apoptosis-and-autophagy-in-glioblastoma-multiforme-role-in-pathogenesis-and-therapeutic-perspective
#8
REVIEW
Elzbieta Pawlowska, Joanna Szczepanska, Magdalena Szatkowska, Janusz Blasiak
Autophagy, cellular senescence, programmed cell death and necrosis are key responses of a cell facing a stress. These effects are partly interconnected, but regulation of their mutual interactions is not completely clear. That regulation seems to be especially important in cancer cells, which have their own program of development and demand more nutrition and energy than normal cells. Glioblastoma multiforme (GBM) belongs to the most aggressive and most difficult to cure cancers, so studies on its pathogenesis and new therapeutic strategies are justified...
March 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29518025/emerging-roles-of-p53-family-members-in-glucose-metabolism
#9
REVIEW
Yoko Itahana, Koji Itahana
Glucose is the key source for most organisms to provide energy, as well as the key source for metabolites to generate building blocks in cells. The deregulation of glucose homeostasis occurs in various diseases, including the enhanced aerobic glycolysis that is observed in cancers, and insulin resistance in diabetes. Although p53 is thought to suppress tumorigenesis primarily by inducing cell cycle arrest, apoptosis, and senescence in response to stress, the non-canonical functions of p53 in cellular energy homeostasis and metabolism are also emerging as critical factors for tumor suppression...
March 8, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29500364/simultaneous-induction-and-blockade-of-autophagy-by-a-single-agent
#10
Karolina Kucharewicz, Magdalena Dudkowska, Anna Zawadzka, Mikolaj Ogrodnik, Andrzej A Szczepankiewicz, Zbigniew Czarnocki, Ewa Sikora
Besides cell death, autophagy and cell senescence are the main outcomes of anticancer treatment. We demonstrate that tacrine-melatonin heterodimer C10, a potent anti-Alzheimer's disease drug, has an antiproliferative effect on MCF-7 breast cancer cells. The main cell response to a 24 h-treatment with C10 was autophagy enhancement accompanied by inhibition of mTOR and AKT pathways. Significantly increased autophagy markers, such as LC3B- and ATG16L-positive vesicles, confirmed autophagy induction by C10. However, analysis of autophagic flux using mCherry-GFP-LC3B construct revealed inhibition of autophagy by C10 at the late-stage...
March 2, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29484762/coroglaucigenin-induces-senescence-and-autophagy-in-colorectal-cancer-cells
#11
Yong-Hao Huang, Jing Lei, Guo-Hui Yi, Feng-Ying Huang, Yue-Nan Li, Cai-Chun Wang, Yan Sun, Hao-Fu Dai, Guang-Hong Tan
OBJECTIVES: Coroglaucigenin (CGN), a natural product isolated from Calotropis gigantean by our research group, has been identified as a potential anti-cancer agent. However, the molecular mechanisms involved remain poorly understood. MATERIALS AND METHODS: Cell viability and cell proliferation were detected by MTT and BrdU assays. Flow cytometry, SA-β-gal assay, western blotting and immunofluorescence were performed to determine CGN-induced apoptosis, senescence and autophagy...
February 27, 2018: Cell Proliferation
https://www.readbyqxmd.com/read/29435183/expression-and-function-of-nuclear-receptor-coactivator-4-isoforms-in-transformed-endometriotic-and-malignant-ovarian-cells
#12
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 HRASV12A , c-MYCT58A , 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
#13
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
#14
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
#15
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
#16
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...
April 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29320480/pharmacological-activation-of-rev-erbs-is-lethal-in-cancer-and-oncogene-induced-senescence
#17
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
#18
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
#19
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
#20
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
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