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https://www.readbyqxmd.com/read/29656006/par-4-dependent-p53-up-regulation-plays-a-critical-role-in-thymoquinone-induced-cellular-senescence-in-human-malignant-glioma-cells
#1
Karthikeyan Subburayan, Faisal Thayyullathil, Siraj Pallichankandy, Anees Rahman, Sehamuddin Galadari
Thymoquinone (TQ), the predominant bioactive constituent present in black cumin (Nigella sativa), exerts tumor suppressive activity against a wide variety of cancer cells. Cellular senescence, characterized by stable and long term loss of proliferative capacity, acts as a potent tumor suppressive mechanism. Here, we provide evidence for the first time that TQ suppresses growth of glioma cells by potentially inducing the expression of prostate apoptosis response-4 (Par-4) tumor suppressor protein. In turn, TQ-induced Par-4 expression triggers cellular senescence, as evidenced by increasing cellular size, β-galactosidase staining, G1 phase arrest, and increased expression of senescence markers such as p53, p21, Rb, and decreased expression of lamin B1, cyclin E and cyclin depended kinase-2 (CDK-2)...
April 12, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29645049/the-inhibitory-effect-of-manuka-honey-on-human-colon-cancer-hct-116-and-lovo-cell-growth-part-1-the-suppression-of-cell-proliferation-promotion-of-apoptosis-and-arrest-of-the-cell-cycle
#2
Sadia Afrin, Francesca Giampieri, Massimiliano Gasparrini, Tamara Y Forbes-Hernández, Danila Cianciosi, Patricia Reboredo-Rodriguez, Adolfo Amici, Josè L Quiles, Maurizio Battino
Numerous investigations have been made on plant phenolic compounds and cancer prevention in recent decades. Manuka honey (MH) represents a good source of phenolic compounds such as luteolin, kaempferol, quercetin, gallic acid and syringic acid. The aim of this work was to evaluate the chemopreventive effects of MH on human colon cancer HCT-116 and LoVo cells. Both cells were exposed to different concentrations of MH (0-20 mg mL-1 for HCT-116 cells and 0-50 mg mL-1 for LoVo cells) for 48 h to measure apoptosis and cell cycle arrest as well as apoptosis and cell cycle regulatory gene and protein expression...
April 12, 2018: Food & Function
https://www.readbyqxmd.com/read/29629647/immunohistochemical-detection-of-p53-pten-rb-and-p16-in-canine-osteosarcoma-using-tissue-microarray
#3
Duncan S Russell, Lauren Jaworski, William C Kisseberth
Although inactivating mutations of tumor suppressor genes are well described in cell lines of canine osteosarcoma (OS), expression of tumor suppressor proteins in spontaneous disease is poorly characterized. We determined the immunohistochemical expression of p53, PTEN, Rb, and p16 in a large cohort of dogs with OS. Formalin-fixed, paraffin-embedded samples of canine OS were analyzed retrospectively. Primary tumor samples from 145 dogs, collected between 2003 and 2008, were evaluated by tissue microarray. Streptavidin-biotin complex immunohistochemistry was performed using monoclonal antibodies for Rb and PTEN and polyclonal antibodies for p16 and p53...
April 1, 2018: Journal of Veterinary Diagnostic Investigation
https://www.readbyqxmd.com/read/29606701/rbl2-p130-is-a-direct-akt-target-and-is-required-to-induce-apoptosis-upon-akt-inhibition-in-lung-cancer-and-mesothelioma-cell-lines
#4
Francesca Pentimalli, Iris M Forte, Luca Esposito, Paola Indovina, Carmelina A Iannuzzi, Luigi Alfano, Caterina Costa, Daniela Barone, Gaetano Rocco, Antonio Giordano
The retinoblastoma (RB) protein family includes RB1/p105, RBL1/p107, and RBL2/p130, which are key factors in cell-cycle regulation and stand at the crossroads of multiple pathways dictating cell fate decisions. The role of RB proteins in apoptosis is controversial because they can inhibit or promote apoptosis depending on the context, on the apoptotic stimuli and on their intrinsic status, impacting on the response to antitumoral treatments. Here we identified RBL2/p130 as a direct substrate of the AKT kinase, a key antiapoptotic factor hyperactive in multiple cancer types...
April 2, 2018: Oncogene
https://www.readbyqxmd.com/read/29605930/a-multiscale-computational-model-for-simulating-the-kinetics-of-protein-complex-assembly
#5
Jiawen Chen, Yinghao Wu
Proteins fulfill versatile biological functions by interacting with each other and forming high-order complexes. Although the order in which protein subunits assemble is important for the biological function of their final complex, this kinetic information has received comparatively little attention in recent years. Here we describe a multiscale framework that can be used to simulate the kinetics of protein complex assembly. There are two levels of models in the framework. The structural details of a protein complex are reflected by the residue-based model, while a lower-resolution model uses a rigid-body (RB) representation to simulate the process of complex assembly...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29587339/gomisin-g-inhibits-the-growth-of-triple-negative-breast-cancer-cells-by-suppressing-akt-phosphorylation-and-decreasing-cyclin-d1
#6
Sony Maharjan, Byoung Kwon Park, Su In Lee, Yoonho Lim, Keunwook Lee, Hyung-Joo Kwon
A type of breast cancer with a defect in three molecular markers such as the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor is called triple-negative breast cancer (TNBC). Many patients with TNBC have a lower survival rate than patients with other types due to a poor prognosis. In this study, we confirmed the anti-cancer effect of a natural compound, Gomisin G, in TNBC cancer cells. Treatment with Gomisin G suppressed the viability of two TNBC cell lines, MDA-MB-231 and MDA-MB-468 but not non-TNBC cell lines such as MCF-7, T47D, and ZR75-1...
March 28, 2018: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29567467/the-critical-role-of-p16-rb-pathway-in-the-inhibition-of-gh3-cell-cycle-induced-by-t-2-toxin
#7
Zainab Fatima, Pu Guo, Deyu Huang, Qirong Lu, Qinghua Wu, Menghong Dai, Guyue Cheng, Dapeng Peng, Yanfei Tao, Muhammad Ayub, Muhammad Tahir Ul Qamar, Muhammad Waqar Ali, Xu Wang, Zonghui Yuan
T-2 toxin is a worldwide trichothecenetoxin and can cause various toxicities.T-2 toxin is involved in G1 phase arrest in several cell lines but molecular mechanism is still not clear. In present study, we used rat pituitary GH3 cells to investigate the mechanism involved in cell cycle arrest against T-2 toxin (40 nM) for 12, 24, 36 and 48 h as compared to control cells. GH3 cells showed a considerable increase in reactive oxygen species (ROS) as well as loss in mitochondrial membrane potential (△Ym) upon exposure to the T-2 toxin...
March 19, 2018: Toxicology
https://www.readbyqxmd.com/read/29566278/down-regulation-of-poteg-predicts-poor-prognosis-in-esophageal-squamous-cell-carcinoma-patients
#8
Ling Wang, Mengqing Li, Yuting Zhan, Xiaojiao Ban, Tingting Zeng, Yinghui Zhu, Jingping Yun, Xin-Yuan Guan, Yan Li
POTE ankyrin domain family, member G (poteg) belongs to POTE family. The POTE family is composed of many proteins which are very closely related and expressed in prostate, ovary, testis, and placenta. Some POTE paralogs are related with some cancers. Here we showed that down-regulation of POTEG was detected in about 60% primary esophageal squamous cell carcinoma (ESCC) tumor tissues. Clinical association studies determined that POTEG down-regulation was significantly correlated with tumor differentiation, lymph nodes metastasis and TNM staging...
March 22, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29563610/a-ras-camkk%C3%AE-ampk%C3%AE-2-pathway-promotes-senescence-by-licensing-post-translational-activation-of-c-ebp%C3%AE-through-a-novel-3-utr-mechanism
#9
Sandip K Basu, Mesfin Gonit, Jacqueline Salotti, Jiji Chen, Atharva Bhat, Myriam Gorospe, Benoit Viollet, Kevin P Claffey, Peter F Johnson
Oncogene-induced senescence (OIS) is an intrinsic tumor suppression mechanism that requires the p53 and RB pathways and post-translational activation of C/EBPβ through the RAS-ERK cascade. We previously reported that in transformed/proliferating cells, C/EBPβ activation is inhibited by G/U-rich elements (GREs) in its 3'UTR. This mechanism, termed "3'UTR regulation of protein activity" (UPA), maintains C/EBPβ in a low-activity state in tumor cells and thus facilitates senescence bypass. Here we show that C/EBPβ UPA is overridden by AMPK signaling...
March 22, 2018: Oncogene
https://www.readbyqxmd.com/read/29552929/benign-fibromyxoid-lesion-of-the-breast-a-distinct-entity-from-benign-spindle-cell-tumors-of-the-mammary-stroma
#10
Christopher J Schwartz, Cynthia A Schandl, Jennifer Morse, Jonathan Ralston, Amy Rapkiewicz, Farbod Darvishian
Myxoid lesions of the breast can be diagnostically challenging entities. We report 4 cases of CD34+ fibromyxoid lesion that have been previously diagnosed as "benign myxoid lesion," "nodular mucinosis," or "mammary myofibroblastoma, myxoid type" on the basis of CD34-positivity. The lesions were microscopically well circumscribed and composed of a paucicellular spindle cell proliferation in a background of myxoid stroma. No epithelial component was identified. The spindle cells showed immunohistochemical reactivity for CD34 and smooth muscle actin...
March 1, 2018: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29552609/rb-interactome-data-and-its-modulations-during-cell-cycle-progression-in-hek-293-cells
#11
Shweta Duggal, Noor Jailkhani, Mukul Kumar Midha, Kanury V S Rao, Ajay Kumar
The Rb protein is a tumor suppressor protein that regulates the key G1S checkpoint consequently blocking the progression of cell cycle into S-phase. Despite its pertinent role in cell cycle regulation, comprehensive information on its interacting partners across cell cycle progression is lacking. Here, we aim to submit a comprehensive set of Rb interactors as the cell progresses from G0 through G1 and S into G2 phase in HEK 293 cell line. Affinity purification of HA-tagged Rb protein along with its interactors was analyzed by mass spectrometry (AP-MS)...
April 2018: Data in Brief
https://www.readbyqxmd.com/read/29546689/disruption-of-leptin-signalling-in-a-mouse-model-of-alzheimer-s-disease
#12
Anna King, Anna Brain, Kelsey Hanson, Justin Dittmann, James Vickers, Carmen Fernandez-Martos
Disruption of leptin signalling has been implicated as playing a role in the development of Alzheimer's disease (AD). Leptin has previously been shown to be affected by amyloid-beta (Aβ)-related signalling; however, pathways that link leptin to the disease pathogenesis have not been determined. To characterize the association between increasing age-dependent Aβ levels with leptin signalling and the vulnerable brain regions in AD, we assessed the mRNA and protein expression profile of leptin and leptin receptor (Ob-Rb) at 9 and 18-month-age in APP/PS1 mice...
March 15, 2018: Metabolic Brain Disease
https://www.readbyqxmd.com/read/29541385/targeting-the-cyclin-dependent-kinase-and-retinoblastoma-axis-overcomes-standard-of-care-resistance-in-braf-v600e-mutant-melanoma
#13
Antoneicka L Harris, Samantha E Lee, Louis K Dawson, Laura A Marlow, Brandy H Edenfield, William F Durham, Thomas J Flotte, Michael Thompson, Daniel L Small, Aidan J Synnott, Svetomir N Markovic, John A Copland
Patient-derived tumor xenograft (PDTX) mouse models were used to discover new therapies for naïve and drug resistant BRAF V600E -mutant melanoma. Tumor histology, oncogenic protein expression, and antitumor activity were comparable between patient and PDTX-matched models thereby validating PDTXs as predictive preclinical models of therapeutic response in patients. PDTX models responsive and non-responsive to BRAF/MEK standard of care (SOC) therapy were used to identify efficacious combination therapies. One such combination includes a CDK4/6 inhibitor that blocks cell cycle progression...
February 16, 2018: Oncotarget
https://www.readbyqxmd.com/read/29535768/neuropilin-1-mediates-keratinocyte-growth-factor-signaling-in-adipose-derived-stem-cells-potential-involvement-in-adipogenesis
#14
Simona Ceccarelli, Cristina Nodale, Enrica Vescarelli, Paola Pontecorvi, Valeria Manganelli, Giovanni Casella, Maria Giuseppina Onesti, Maurizio Sorice, Ferdinando Romano, Antonio Angeloni, Cinzia Marchese
Adipogenesis is regulated by a complex network of molecules, including fibroblast growth factors. Keratinocyte growth factor (KGF) has been previously reported to promote proliferation on rat preadipocytes, although the expression of its specific receptor, FGFR2-IIIb/KGFR, is not actually detected in mesenchymal cells. Here, we demonstrate that human adipose-derived stem cells (ASCs) show increased expression of KGF during adipogenic differentiation, especially in the early steps. Moreover, KGF is able to induce transient activation of ERK and p38 MAPK pathways in these cells...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29522490/suppression-of-cell-growth-migration-and-drug-resistance-by-ethanolic-extract-of-antrodia-cinnamomea-in-human-lung-cancer-a549-cells-and-c57bl-6j-allograft-tumor-model
#15
Chi-Han Wu, Fon-Chang Liu, Chun-Hsu Pan, Ming-Tsung Lai, Shou-Jen Lan, Chieh-Hsi Wu, Ming-Jyh Sheu
The purpose of this study was to investigate the inhibitory activities of ethanolic extracts from Antrodia cinnamomea (EEAC) on lung cancer. Cell proliferation and cell cycle distribution were analyzed using (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay and flow cytometry, respectively. Wound-healing assay, Western blotting, and a murine tumor model were separately used to examine cell migration, protein expression, and tumor repression. Our results showed that EEAC induced cell cycle arrest at the G0/G1 phase resulting decreased cell viability in A549 cells...
March 9, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29521624/functional-genomics-of-lipid-metabolism-in-the-oleaginous-yeast-rhodosporidium-toruloides
#16
Samuel T Coradetti, Dominic Pinel, Gina Geiselman, Masakazu Ito, Stephen Mondo, Morgann C Reilly, Ya-Fang Cheng, Stefan Bauer, Igor Grigoriev, John M Gladden, Blake A Simmons, Rachel Brem, Adam P Arkin, Jeffrey M Skerker
The basidiomycete yeast Rhodosporidium toruloides (a.k.a. Rhodotorula toruloides ) accumulates high concentrations of lipids and carotenoids from diverse carbon sources. It has great potential as a model for the cellular biology of lipid droplets and for sustainable chemical production. We developed a method for high-throughput genetics (RB-TDNAseq), using sequence-barcoded Agrobacterium tumefaciens T-DNA insertions. We identified 1337 putative essential genes with low T-DNA insertion rates. We functionally profiled genes required for fatty acid catabolism and lipid accumulation, validating results with 35 targeted deletion strains...
March 9, 2018: ELife
https://www.readbyqxmd.com/read/29517104/microrna%C3%A2-448-inhibits-the-progression-of-retinoblastoma-by-directly-targeting-rock1-and-regulating-pi3k-akt-signalling-pathway
#17
Shen Wu, Nanping Ai, Qian Liu, Jingxue Zhang
Retinoblastoma (RB) is the most common primary intraocular malignancy during infancy and childhood worldwide. Numerous microRNAs (miRNAs) contribute to RB initiation and progression through the regulation of cell proliferation, cycle, apoptosis, migration, invasion and metastasis. Therefore, further investigation concerning the expression, roles and associated mechanisms of RB‑related miRNAs may be beneficial to develop novel strategies for patients with this malignancy. Recently, miRNA‑448 (miR‑448) has been reported to be aberrantly expressed and to play an important role in several types of human cancer...
March 8, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29514796/osteoblast-secreted-factors-mediate-dormancy-of-metastatic-prostate-cancer-in-the-bone-via-activation-of-the-tgf%C3%AE-riii-p38mapk-ps249-t252rb-pathway
#18
Li-Yuan Yu-Lee, Guoyu Yu, Yu-Chen Lee, Song-Chang Lin, Jing Pan, Tianhong Pan, Kai-Jie Yu, Bin Liu, Chad J Creighton, Jaime Rodriguez-Canales, Pamela Andrea Villalobos, Ignacio Ivan Wistuba, Eulàlia de Nadal, Francesc Posas, Gary E Gallick, Sue-Hwa Lin
Bone metastasis from prostate cancer (PCa) can occur years after prostatectomy, due to reactivation of dormant disseminated tumor cells (DTC) in the bone, yet the mechanism by which DTC are initially induced into a dormant state in the bone remains to be elucidated. We show here that the bone microenvironment confers dormancy to C4-2B4 PCa cells, as they become dormant when injected into mouse femurs but not under the skin. Live-cell imaging of dormant cells at the single cell level revealed that conditioned medium from differentiated, but not undifferentiated osteoblasts induced C4-2B4 cellular quiescence, suggesting that differentiated osteoblasts present locally around the tumor cells in the bone conferred dormancy to PCa cells...
March 7, 2018: Cancer Research
https://www.readbyqxmd.com/read/29512682/cyclic-mechanical-tension-reinforces-dna-damage-and-activates-the-p53-p21-rb-pathway-to-induce-premature-senescence-of-nucleus-pulposus-cells
#19
Chencheng Feng, Minghui Yang, Yang Zhang, Minghong Lan, Bo Huang, Huan Liu, Yue Zhou
Intervertebral disc (IVD) degeneration (IDD) is a widely recognized contributor to low back pain. Mechanical stress is a crucial etiological factor of IDD. During the process of IDD, a vicious circle is formed between abnormal mechanical stress and the damage of disc structure and function. Notably, the pathological process of IDD is mediated by the phenotypic shift of IVD cells from an extracellular matrix anabolic phenotype to a catabolic and pro-inflammatory phenotype. Therefore, the effects of mechanical stress on the initiation and progression of IDD depend on the mechanobiology of IVD cells...
February 28, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29506474/anti-apoptotic-effects-of-igf-i-on-mortality-and-dysmorphogenesis-in-tbx5-deficient-zebrafish-embryos
#20
Tzu-Chun Tsai, Chun-Che Shih, Hsin-Ping Chien, An-Hang Yang, Jenn-Kan Lu, Jen-Her Lu
BACKGROUND: Tbx5 deficiency in zebrafish causes several abnormal phenotypes of the heart and pectoral fins. It has been reported that exogenous human growth hormone can enhance expression of downstream mediators in the growth hormone and insulin-like growth factor I (IGF-I) pathway and partially restore dysmorphogenesis in tbx5 morphants. This study aimed to further evaluate the effects of IGF-I on cell apoptosis and dysmorphogenesis in zebrafish embryos deficient for tbx5. RESULTS: Among the five studied groups of zebrafish embryos (wild-type embryos [WT], tbx5 morphants [MO], mismatched tbx5 morpholino-treated wild-type embryos [MIS], IGF-I-treated wild-type embryos [WTIGF1], and IGF-I-treated tbx5 morphants [MOIGF1]), the expression levels of the ifg1, igf1-ra, ifg-rb, erk1, and akt2 genes as well as the ERK and AKT proteins were significantly reduced in the MO group, but were partially restored in the MOIGF1 group...
March 5, 2018: BMC Developmental Biology
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