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https://www.readbyqxmd.com/read/28726723/mertensene-a-halogenated-monoterpene-induces-g2-m-cell-cycle-arrest-and-caspase-dependent-apoptosis-of-human-colon-adenocarcinoma-ht29-cell-line-through-the-modulation-of-erk-1-2-akt-and-nf-%C3%AE%C2%BAb-signaling
#1
Safa Tarhouni-Jabberi, Ons Zakraoui, Efstathia Ioannou, Ichrak Riahi-Chebbi, Meriam Haoues, Vassilios Roussis, Riadh Kharrat, Khadija Essafi-Benkhadir
Conventional treatment of advanced colorectal cancer is associated with tumor resistance and toxicity towards normal tissues. Therefore, development of effective anticancer therapeutic alternatives is still urgently required. Nowadays, marine secondary metabolites have been extensively investigated due to the fact that they frequently exhibit anti-tumor properties. However, little attention has been given to terpenoids isolated from seaweeds. In this study, we isolated the halogenated monoterpene mertensene from the red alga Pterocladiella capillacea (S...
July 20, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28725489/bmp-2-induces-emt-and-breast-cancer-stemness-through-rb-and-cd44
#2
Peide Huang, Anan Chen, Weiyi He, Zhen Li, Guanglin Zhang, Zhong Liu, Ge Liu, Xueting Liu, Shuilian He, Gang Xiao, Feicheng Huang, Jan Stenvang, Nils Brünner, An Hong, Ju Wang
Bone morphogenetic protein 2 (BMP-2) has been reported to facilitate epithelial-to-mesenchymal transition (EMT) and bone metastasis in breast cancer xenograft models. To investigate the role of BMP-2 in the development of breast cancer stem cells (BCSCs), and to further elucidate the mechanisms underlying its influence on breast cancer metastasis, we conducted a comprehensive molecular study using breast cancer cell lines and clinical samples. Our results showed that downregulation of Rb by BMP-2 was associated with ubiquitin-mediated degradation activated by phosphorylation of Rb via the PI3K/AKT signal pathway...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28723241/the-effects-of-stretch-activation-on-ionic-selectivity-of-the-trek-2-k2p-k-channel
#3
Ehsan Nematian-Ardestani, Viwan Jarerattanachat, Prafulla Aryal, Mark S P Sansom, Stephen J Tucker
The TREK-2 (KCNK10) K2P potassium channel can be regulated by variety of polymodal stimuli including pressure. In a recent study, we demonstrated that this mechanosensitive K(+) channel responds to changes in membrane tension by undergoing a major structural change from its 'down' state to the more expanded 'up' state conformation. These changes are mostly restricted to the lower part of the protein within the bilayer, but are allosterically coupled to the primary gating mechanism located within the selectivity filter...
July 19, 2017: Channels
https://www.readbyqxmd.com/read/28722352/serpine-1-induces-alveolar-type-ii-cell-senescence-through-activating-p53-p21-rb-pathway-in-fibrotic-lung-disease
#4
Chunsun Jiang, Gang Liu, Tracy Luckhardt, Veena Antony, Yong Zhou, A Brent Carter, Victor J Thannickal, Rui-Ming Liu
Senescence of alveolar type 2 (ATII) cells, progenitors of the alveolar epithelium, is implicated in the pathogeneses of idiopathic pulmonary fibrosis (IPF), an aging-related progressive fatal lung disorder with unknown etiology. The mechanism underlying ATII cell senescence in fibrotic lung diseases, however, remains poorly understood. In this study, we report that ATII cells in IPF lungs express higher levels of serpine 1, also known as plasminogen activator inhibitor 1 (PAI-1), and cell senescence markers p21 and p16, compared to ATII cells in control lungs...
July 19, 2017: Aging Cell
https://www.readbyqxmd.com/read/28718726/effects-of-the-notch1-signaling-pathway-on-human-lung-cancer-a549-cells
#5
Yun Zeng, Bijian Yin, Xinwei Wang, Guohao Xia, Zhengjie Shen, Wenzhe Gu, Mianhua Wu
PURPOSE: To evaluate the effects of the Notch1 signaling pathway on human lung cancer A549 cells. MATERIALS AND METHODS: A549 cells were transfected with recombinant plasmids. Cell proliferation was detected by MTT assay. A tumor-bearing mouse model was established for intratumoral gene injection. Apoptosis-related factors were detected by immunohistochemical assay. Caspase-8, caspase-3, caspase-9, PI3K, pAkt and pSTAT3 expressions were detected by Western blotting...
July 18, 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28713162/abt-263-induces-g1-g0-phase-arrest-apoptosis-and-autophagy-in-human-esophageal-cancer-cells-in-vitro
#6
Qing-Huan Lin, Fu-Chang Que, Chun-Ping Gu, De-Sheng Zhong, Dan Zhou, Yi Kong, Le Yu, Shu-Wen Liu
Both the anti- and pro-apoptotic members of the Bcl-2 family are regulated by a conserved Bcl-2 homology (BH3) domain. ABT-263 (Navitoclax), a novel BH3 mimetic and orally bioavailable Bcl-2 family inhibitor with high affinity for Bcl-xL, Bcl-2 and Bcl-w has entered clinical trials for cancer treatment. But the anticancer mechanisms of ABT-263 have not been fully elucidated. In this study we investigated the effects of ABT-263 on human esophageal cancer cells in vitro and to explore its anticancer mechanisms...
July 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28679059/role-and-potential-targeting-of-hepatic-apurinic-apyrimidinic-endonuclease-1-and-cyclin-dependent-kinase-4-in-hepatocellular-carcinoma
#7
Kadry Sadek, Tarek Abouzed, Sherif Nasr, Moustafa Shukry
Apurinic/apyrimidinic endonuclease/redox element 1 (APE1/Ref-1) is a pervasive multifunctional protein required in the DNA base extraction repair (BER) pathway and a noteworthy reducing-oxidizing (redox) factor that upgrades the authoritative of various transcription components to DNA. Cyclin-dependent kinases (CDKs) assume a key part in directing the movement of the cell-cycle. The present study evaluates the synergistic efficacy of using licochalcone B (LCB) and fullerene C60 (FnC60) nanoparticles against diethylnitrosamine (DEN)-induced hepatocarcinoma (HCC) in rats...
July 5, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28672917/downregulation-of-p16-promotes-cigarette-smoke-extract-induced-vascular-smooth-muscle-cell-proliferation-via-preventing-g1-s-phase-transition
#8
Tao Guo, Xiangping Chai, Qiming Liu, Wen Peng, Zhenyu Peng, Yuzhong Cai
The proliferation of vascular smooth muscle cells (VSMCs) serves an important role in cigarette smoking-associated vascular diseases; however, the underlying mechanisms responsible for this remain unclear. The aim of the present study was to elucidate the role of P16 in cigarette smoke extract (CSE)-induced VSMC proliferation and the underlying mechanism responsible. Human aortic smooth muscle cells (HAOSMCs) were exposed to CSE, and an MTT assay and flow cytometry were performed to evaluate cell proliferation and cell cycle distribution...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28670489/heat-shock-protein-70-2-hsp70-2-a-novel-cancer-testis-antigen-that-promotes-growth-of-ovarian-cancer
#9
Namita Gupta, Nirmala Jagadish, Avadhesha Surolia, Anil Suri
Heat shock protein 70-2 (HSP70-2) is known to be involved in tumor progression. However, its molecular role and mechanism in epithelial ovarian cancer (EOC) remains unknown. In the present investigation, we examined the role of HSP70-2 in cell cycle, apoptosis and epithelial mesenchymal transition pathways in EOC cells in in vitro and in-vivo xenograft mouse model. To investigate the role of HSP70-2 in ovarian cancer, plasmid driven short hairpin RNA approach was used to examine HSP70-2 gene and protein expression in ovarian cancer cell line A-10 (origin: serous papillary cystadenocarcinoma), Caov-3 (origin: adenocarcinoma) and SKOV3 (origin: adenocarcinoma; derived from metastatic site: ascites) by RT-PCR, quantitative-PCR, immunohistochemistry and Western blotting...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28667245/a-screen-for-inducers-of-bhlh-activity-identifies-pitavastatin-as-a-regulator-of-p21-rb-phosphorylation-and-e2f-target-gene-expression-in-pancreatic-cancer
#10
Nicholas Villarino, Lia Signaevskaia, Jaco van Niekerk, Rachel Medal, Heejung Kim, Reyhaneh Lahmy, Kathleen Scully, Anthony Pinkerton, SangWun Kim, Andrew Lowy, Pamela Itkin-Ansari
The average survival for patients with Pancreatic Ductal Adenocarcinoma (PDA) is merely 6 months, underscoring the need for new therapeutic approaches. During PDA progression, pancreatic acinar cells lose activity of the ClassI/II bHLH factors that regulate quiescence. We previously found that promoting transcriptional activity of the Class I bHLH factor E47 in highly aggressive PDA cells induced stable growth arrest in vitro and in vivo. To translate these findings for clinical utility, we developed a high throughput screening platform to identify small molecule inducers of Class I/II bHLH activity...
June 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28655788/prmt1-mediated-translation-regulation-is-a-crucial-vulnerability-of-cancer
#11
Jessie Hao-Ru Hsu, Benjamin Hubbell-Engler, Guillaume Adelmant, Jialiang Huang, Cailin E Joyce, Francisca Vazquez, Barbara A Weir, Philip Montgomery, Aviad Tsherniak, Andrew O Giacomelli, Jennifer A Perry, Jennifer Trowbridge, Yuko Fujiwara, Glenn S Cowley, Huafeng Xie, Woojin Kim, Carl D Novina, William C Hahn, Jarrod A Marto, Stuart H Orkin
Through an shRNA screen we identified the protein arginine methyltransferase Prmt1 as a vulnerable intervention point in murine p53/Rb-null osteosarcomas, the human counterpart of which lacks effective therapeutic options. Depletion of Prmt1 in p53-deficient cells impaired tumor initiation and maintenance in vitro and in vivo Mechanistic studies reveal that translation-associated pathways were enriched for Prmt1 downstream targets, implicating Prmt1 in translation control. In particular, loss of Prmt1 led to a decrease in arginine methylation of the translation initiation complex, thereby disrupting its assembly and inhibiting translation...
June 27, 2017: Cancer Research
https://www.readbyqxmd.com/read/28653901/gankyrin-promotes-the-proliferation-of-gastric-cancer-and-is-associated-with-chemosensitivity
#12
Yue-Can Zeng, Dan Sun, Wen-Hui Li, Jing Zhao, Yan Xin
Although gankyrin is involved in the tumorigenicity and metastasis of some malignancies, the role of gankyrin in gastric cancer is not clear. In this study, we evaluated the function and mechanism of gankyrin in gastric cancer. The effects of gankyrin on gastric cancer growth, proliferation, and chemosensitivity were determined. Gankyrin expression was significantly increased in gastric cancer compared to non-cancerous tissues. This expression significantly enhanced cancer cell proliferation and growth in vitro and in vivo...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28653201/chondrolipoma-of-the-breast-as-a-rare-variant-of-myofibroblastoma-an-immunohistochemical-study-of-two-cases
#13
Masayuki Shintaku, Yoshihiro Yamamoto, Fumihiko Kono, Toshiyuki Kitai, Wakako Tsuji, Fumiaki Yotsumoto, Ryoji Kushima
Chondrolipoma of the breast is a very rare tumor whose histogenesis remains obscure. We report two cases (56-year-old and 43-year-old women) and present the results of an immunohistochemical study which strongly suggests that this tumor is a variant of myofibroblastoma. The tumors predominantly consisted of lipoma-like, mature adipose tissue, and many islands of hyaline cartilage. A proliferation of spindle cells associated with the deposition of collagen fibers was also seen. On immunohistochemical examination, spindle cells showed cytoplasmic reactivity for vimentin, desmin, bcl-2, and α-smooth muscle actin, as well as nuclear reactivity for estrogen receptor (ER) and progesterone receptor (PgR)...
June 26, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28650445/a-distinct-function-of-the-retinoblastoma-protein-in-the-control-of-lipid-composition-identified-by-lipidomic-profiling
#14
H Muranaka, A Hayashi, K Minami, S Kitajima, S Kohno, Y Nishimoto, N Nagatani, M Suzuki, L A N Kulathunga, N Sasaki, N Okada, T Matsuzaka, H Shimano, H Tada, C Takahashi
Here, by combining lipidomics with transcriptome analysis, we demonstrate that Rb depletion in mouse embryonic fibroblastss induces significant alterations in their lipid composition. We discovered that Rb depletion induced increase in lysophosphatidylserine, diacylglycerol (DAG), fatty acid (FA), acylcarnitine, phosphatidylcholine (PC), arachidonoyl ethanolamine, and decrease in phosphatidylglycerol, monoacylglycerol, without change in total lipid per protein levels. Analysis of the acyl chain composition of DAG, PC and phosphatidylserine revealed increase of saturated and mono-unsaturated acyl chains with specific carbon chain length...
June 26, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28647672/therapeutic-targeting-of-nuclear-export-inhibition-in-lung-cancer
#15
Arjun Gupta, Jessica M Saltarski, Michael A White, Pier P Scaglioni, David E Gerber
Intracellular compartmentalization and trafficking of molecules plays a critical role in complex and essential cellular processes. In lung cancer and other malignancies, aberrant nucleocytoplasmic transport of tumor suppressor proteins and cell cycle regulators results in tumorigenesis and inactivation of apoptosis. Pharmacologic targeting of this process, termed selective inhibition of nuclear export (SINE), has demonstrated anti-tumor efficacy in preclinical models and human clinical trials. Exportin-1 (XPO1)-which serves as the sole exporter of several tumor suppressor proteins and cell cycle regulators, including retinoblastoma (Rb), adenomatous polyposis coli (APC), p53, p73, p21, p27, FOXO, STAT3, IKB, topoisomerase II and PAR-4-is the principal focus of SINE drug development...
June 21, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28637687/inhibition-of-cdk4-6-by-palbociclib-significantly-extends-survival-in-medulloblastoma-patient-derived-xenograft-mouse-models
#16
Michelle L Cook Sangar, Laura A Genovesi, Madison W Nakamoto, Melissa J Davis, Sue E Knoblaugh, Pengxiang Ji, Amanda Millar, Brandon Wainwright, James M Olson
  <p>Bioinformatics analysis followed by in vivo studies in patient-derived xenograft models were used to identify and validate CDK 4/6 inhibition as an effective therapeutic strategy for medulloblastoma, particularly Group 3 MYC-amplified tumors which have the worst clinical prognosis.</p> <br />Experimental Design: <p>A protein interaction network derived from a Sleeping Beauty mutagenesis model of medulloblastoma was used to identify potential novel therapeutic targets.  The top hit from this analysis was validated in vivo using patient-derived xenograft models of medulloblastoma implanted subcutaneously in the flank and orthotopically in the cerebellum of mice...
June 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28637359/decreased-paraoxonase-2-enzymatic-activity-in-monocyte-macrophages-cells-a-comparative-in-vivo-and-in-vitro-study-for-diabetes
#17
D Lixandru, P Alexandru, A Mihai, A Roşca, C Ionescu-Tîrgovişte, L I Braşoveanu, B Manuel-Y-Keenoy
Aim To investigate peripheral blood monocytes/macrophages (Mo/Mø) paraoxonase2 (PON2) in diabetes and the factors modulating its activity. Methods 118 patients with newly diagnosed uncomplicated type 2 diabetes mellitus were compared regarding clinical, biochemical and oxidative stress parameters with 80 healthy subjects. The capacity of the peripheral blood mononuclear cells (PBMNC) to release pro-oxidants and to neutralize them was determined by measuring the respiratory burst (RB) and the intracellular antioxidant enzyme PON2...
June 21, 2017: Free Radical Research
https://www.readbyqxmd.com/read/28636114/set-i2pp2a-overexpression-induces-phenotypic-molecular-and-metabolic-alterations-in-an-oral-keratinocyte-cell-line
#18
Lays M Sobral, Ricardo D Coletta, Luciane C Alberici, Carlos Curti, Andréia Machado Leopoldino
The multifunctional SET/I2PP2A protein is known to be overexpressed in head and neck squamous cell carcinoma. However, SET has been reported to have apparently conflicting roles in promoting cancer cell survival under oxidative stress conditions and preventing invasion and metastasis, complicating efforts to understand the contribution of SET to carcinogenesis. In the present study, we overexpressed SET in a spontaneously immortalized oral keratinocyte cell line (NOK-SI SET) and demonstrated that SET up-regulation alone was sufficient to transform cells...
June 21, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28631603/a-single-point-mutation-in-tomato-spotted-wilt-virus-nss-protein-is-sufficient-to-overcome-tsw-gene-mediated-resistance-in-pepper
#19
Asztéria Almási, Katalin Nemes, Zsófia Csömör, István Tóbiás, László Palkovics, Katalin Salánki
The nonstructural protein (NSs) of Tomato spotted wilt virus (TSWV) was previously identified as an avirulence determinant for Tsw-based resistance on pepper. The NSs of wild-type (WT) and resistance-breaking (RB) TSWV strains isolated in Hungary had only two amino acid substitutions (104, 461). We have analysed the ability of the NSs and their point mutant variants to trigger Tsw-mediated hypersensitive responses and RNA silencing suppressor (RSS) activity in patch assays. We identified a single amino acid change at position 104 (T-A) that was responsible for the necrosis induction or loss, while a significant difference was not detected in the RSS activity of the two parental strains...
June 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28630280/ki-67-contributes-to-normal-cell-cycle-progression-and-inactive-x-heterochromatin-in-p21-checkpoint-proficient-human-cells
#20
Xiaoming Sun, Aizhan Bizhanova, Timothy D Matheson, Jun Yu, Julie L Zhu, Paul D Kaufman
Ki-67 protein is widely used as a tumor proliferation marker. However, whether Ki-67 affects cell cycle progression has been controversial. Here, we demonstrate that depletion of Ki-67 in human hTERT-RPE1, WI-38, IMR90, hTERT-BJ cell lines and primary fibroblast cells slowed entry into S phase and coordinately downregulated genes related to DNA replication. Some gene expression changes were partially relieved in Ki-67-depleted hTERT-RPE1 cells by co-depletion of the Rb checkpoint protein, but more thorough suppression of the transcriptional and cell cycle defects was observed upon depletion of cell cycle inhibitor p21...
June 19, 2017: Molecular and Cellular Biology
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