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Biochemical Pharmacology

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https://www.readbyqxmd.com/read/30639456/mir-142-5p-enhances-cisplatin-induced-apoptosis-in-ovarian-cancer-cells-by-targeting-multiple-anti-apoptotic-genes
#1
Xiaodi Li, Wei Chen, Yuhao Jin, Renxing Xue, Jiancheng Su, Zekun Mu, Jiamin Li, Songshan Jiang
Chemotherapy is the preferred treatment for advanced ovarian cancer, but the 5-year survival rate remains low partly because of the development of drug resistance. Although it has been reported that X-linked inhibitor of apoptosis (XIAP) causes more severe chemoresistance in ovarian cancer cells and is highly expressed in chemoresistant ovarian cancer, the molecular mechanism underlying this dysregulation is unknown. The purpose of this study was to identify microRNAs (miRNAs) that bind to the 3' untranslated region (3'UTR) of XIAP and have a role in chemoresistance in ovarian cancer...
January 10, 2019: Biochemical Pharmacology
https://www.readbyqxmd.com/read/30639455/the-nuclear-receptor-rev-erb%C3%AE-participates-in-circadian-regulation-of-ugt2b-enzymes-in-mice
#2
Tianpeng Zhang, Lianxia Guo, Fangjun Yu, Min Chen, Baojian Wu
Circadian clock is known to modulate phase I metabolism, however whether and how the phase II enzymes UDP-glucuronosyltransferases (UGTs) are regulated by circadian clock are largely unknown. In this study, we aimed to investigate a potential role of the clock gene Rev-erbα in regulation of Ugt2b enzymes. Ugt2b mRNA and protein expression in mouse livers were determined at a 4-h interval around the clock. Ugt2b activity was probed using morphine as a specific substrate. Regulation of Ugt2b by Rev-erbα was investigated using mouse hepatoma Hepa-1c1c7 cells and Rev-erbα knock-out (Rev-erbα-/- ) mice...
January 10, 2019: Biochemical Pharmacology
https://www.readbyqxmd.com/read/30639262/anti-tumor-effect-of-sulfasalazine-in-neuroblastoma
#3
Marie R Mooney, Dirk Geerts, Eric J Kort, André S Bachmann
Neuroblastoma (NB) is a tumor arising from the sympathetic nervous system during infancy and early childhood. High-risk patients who relapse often fail to respond to further therapy, which results in 5-year survival rate for this patient group below 5%. Therefore, there continues to be an urgent need for innovative treatments. Recently, we found that sulfasalazine (SSZ), an FDA-approved drug for the treatment of rheumatoid arthritis and ulcerative colitis induces anti-proliferative effects in NB tumor cells...
January 9, 2019: Biochemical Pharmacology
https://www.readbyqxmd.com/read/30633870/sarm-from-immune-regulator-to-cell-executioner
#4
Michael Carty, Andrew G Bowie
SARM is the fifth and most conserved member of the Toll/Il-1 Receptor (TIR) adaptor family. However, unlike the other TIR adaptors, MyD88, Mal, TRIF and TRAM, SARM does not participate in transducing signals downstream of TLRs. By contrast SARM inhibits TLR signalling by interacting with the adaptors TRIF and MyD88. In addition, SARM also has positive roles in innate immunity by activating specific transcriptional programs following immune challenge. SARM has a pivotal role in activating different forms of cell death following cellular stress and viral infection...
January 8, 2019: Biochemical Pharmacology
https://www.readbyqxmd.com/read/30633869/growth-of-breast-cancer-cells-by-leptin-is-mediated-via-activation-of-the-inflammasome-critical-roles-of-estrogen-receptor-signaling-and-reactive-oxygen-species-production
#5
Pawan Kumar Raut, Sang-Hyun Kim, Dong Young Choi, Gil-Saeng Jeong, Pil-Hoon Park
Leptin, a hormone primarily derived from adipose tissue, is known to induce tumor growth, but its underlying mechanisms of action are not clearly understood. Inflammasomes, acting as signaling platforms for controlling inflammatory responses, modulate tumor growth in a complicated manner. In this study, we investigated the role of inflammasomes in leptin-induced growth of breast cancer cells. Herein, we showed that leptin activated NLRP3 inflammasomes in MCF-7 breast cancer cells, as determined by activation of caspase-1, maturation of interleukin-1β, and increased expression of the inflammasome components, including NLRP3 and ASC...
January 8, 2019: Biochemical Pharmacology
https://www.readbyqxmd.com/read/30629941/potentialization-of-anticancer-agents-by-identification-of-new-chemosensitizers-active-under-hypoxia
#6
Marx Sébastien, VAN Gysel Mégane, Breuer Aurélie, Dal Maso Thomas, Michiels Carine, Wouters Johan, L E Calve Benjamin
Hypoxia is one of the most important biological phenomena that influences cancer agressiveness and chemotherapy resistance. Cancer cells display dysregulated pathways notably resulting from oncogene expression. Tumors also show modifications in extracellular pH, extracellular matrix remodeling, neo-angiogenesis, hypoxia compared to normal tissues. Classically, the conventional anticancer therapies are efficient in cancer cells in normoxic conditions but under hypoxia, chemoresistance may occur. The addition of compounds that potentiate their activity in low oxygen environment could be a strategy to counteract this resistance...
January 7, 2019: Biochemical Pharmacology
https://www.readbyqxmd.com/read/30625299/involvement-of-cell-oxidant-status-and-redox-state-in-the-increased-non-enzymatic-ethanol-oxidation-by-the-regenerating-rat-liver
#7
Rolando Hernández-Muñoz, Martha Lucinda Contreras-Zentella
Ethanol administration is capable of inhibiting or delaying the partial hepatectomy (PH)-induced liver regeneration, probably altering liver metabolism by means of its oxidative metabolism. Since the regenerating liver has increased capacity for oxidizing ethanol, the present study was aimed to address the contribution of the ethanol-oxidizing metabolic pathways in the regenerating liver cells. Isolated hepatocytes were prepared from control livers and from animals subjected to two-thirds PH. In both preparations, ethanol oxidation was largely increased by incubation with glucose and was highly sensitive to inhibitors of ethanol-oxidizing enzymatic pathways (alcohol dehydrogenase, catalase and cytochrome P-4502E1 activities)...
January 6, 2019: Biochemical Pharmacology
https://www.readbyqxmd.com/read/30615863/natural-modulators-of-the-hallmarks-of-immunogenic-cell-death
#8
REVIEW
Flavia Radogna, Mario Dicato, Marc Diederich
Natural compounds act as immunoadjuvants as their therapeutic effects trigger cancer stress response and release of damage-associated molecular patterns (DAMPs). These reactions occur through an increase in the immunogenicity of cancer cells that undergo stress followed by immunogenic cell death (ICD). These processes result in a chemotherapeutic response with a potent immune-mediating reaction. Natural compounds that induce ICD may function as an interesting approach in converting cancer into its own vaccine...
January 4, 2019: Biochemical Pharmacology
https://www.readbyqxmd.com/read/30615862/calcineurin-p38mapk-hsp27-dependent-pathways-are-involved-in-the-attenuation-of-postischemic-mitochondrial-injury-afforded-by-sodium-bicarbonate-co-transporter-nbce1-inhibition
#9
Alejandro Ciocci Pardo, Luisa F González Arbeláez, Juliana C Fantinelli, Ernesto A Aiello, Susana M Mosca
The electrogenic sodium bicarbonate co-transporter isoform 1 (NBCe1) plays an important role in ischemia-reperfusion injury. The cardioprotective action of an antibody directed to the extracellular loop 3 (a-L3) of NBCe1 was previously demonstrated by us. However, the role of a-L3 on mitochondrial post-ischemic alterations has not yet been determined. In this study, we aimed to elucidate the effects of a-L3 on post-ischemic mitochondrial state and dynamics analysing the involved mechanisms. Isolated rat hearts were assigned to the following groups: 1) Non-ischemic control (NIC): 110 min of perfusion; 2) Ischemic control (IC): 30 min of global ischemia and 60 min of reperfusion (R); 3) a-L3: a-L3 was administered during the initial 10 min of R; 4) SB + a-L3: SB202190 (p38MAPK inhibitor) plus a-L3...
January 4, 2019: Biochemical Pharmacology
https://www.readbyqxmd.com/read/30611738/systemic-administration-of-serotonin-exacerbates-abdominal-pain-and-colitis-via-interaction-with-the-endocannabinoid-system
#10
Maciej Salaga, Agata Binienda, Fabiana Piscitelli, Anna Mokrowiecka, Adam I Cygankiewicz, Roberta Verde, Ewa Malecka-Panas, Radzislaw Kordek, Wanda M Krajewska, Vincenzo Di Marzo, Jakub Fichna
BACKGROUND AND AIMS: Molecular basis of abdominal pain in IBD is not fully characterized. Serotonin (5-HT) increases visceral pain severity and contributes to exacerbation of inflammation. Moreover, it is well established that decreased anandamide (AEA) signaling in the gut increases visceral pain severity. The aim of this study was to investigate the interplay between 5-HT and endocannabinoid signaling in colitis. METHODS: We used 3% DSS in drinking water to induce colitis in mice...
January 3, 2019: Biochemical Pharmacology
https://www.readbyqxmd.com/read/30582898/developments-in-bile-salt-based-therapies-a-critical-overview
#11
REVIEW
Joanne M Donkers, Reinout L P Roscam Abbing, Stan F J van de Graaf
Bile acids, amphipathic molecules known for their facilitating role in fat absorption, are also recognized as signalling molecules acting via nuclear and membrane receptors. Of the bile acid-activated receptors, the Farnesoid X Receptor (FXR) and the G protein-coupled bile acid receptor-1 (Gpbar1 or TGR5) have been studied most extensively. Bile acid signaling is critical in the regulation of bile acid metabolism itself, but it also plays a significant role in glucose, lipid and energy metabolism. Activation of FXR and TGR5 leads to reduced hepatic bile salt load, improved insulin sensitivity and glucose regulation, increased energy expenditure, and anti-inflammatory effects...
December 21, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/30579838/schedule-dependent-synergistic-effects-of-5-fluorouracil-and-selumetinib-in-kras-or-braf-mutant-colon-cancer-models
#12
Hye Yeon Jang, Do Hyung Kim, Haeng Jung Lee, Won Dong Kim, Seog-Young Kim, Jung Jin Hwang, Seung Jin Lee, Dae Hyuk Moon
Combination of MEK inhibitor and 5-FU had showed limited efficacy in clinical trials. We previously reported that acquired resistance to 5-FU was related with continued activation of salvage pathway. Here we investigated whether combination of 5-FU and a MEK inhibitor had treatment sequence-dependent synergistic effects in KRAS or BRAF mutant colon cancer models. Treatment with 5-FU followed by selumetinib (FS) induced highest cell death and synergy compared with reverse (SF) and concomitant (cFS) treatment in six cell lines...
December 20, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/30578766/an-n-6-methyladenosine-at-the-transited-codon-273-of-p53-pre-mrna-promotes-the-expression-of-r273h-mutant-protein-and-drug-resistance-of-cancer-cells
#13
Mohammad B Uddin, Kartik R Roy, Salman B Hosain, Sachin K Khiste, Ronald A Hill, Seetharama D Jois, Yunfeng Zhao, Alan J Tackett, Yong-Yu Liu
Mutant p53 proteins that promote cancer cell invasive growth, metastasis and drug resistance emerge as therapeutic targets. Previously, we reported that suppression of ceramide glycosylation restored wild-type p53 protein and tumor suppressing function in cancer cells heterozygously carrying p53 R273H, a hot-spot missense mutation; however, the mechanisms underlying the control of mutant protein expression remain elusive. Herein, we report that an N6 -methyladenosine (m6 A) at the point-mutated codon 273 (G>A) of p53 pre-mRNA determines the mutant protein expression...
December 19, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/30578765/contrasting-effects-of-microtubule-destabilizers-versus-stabilizers-on-induction-of-death-in-g1-phase-of-the-cell-cycle
#14
Magdalena Delgado, Alicja Urbaniak, Timothy C Chambers
Microtubule targeting agents (MTAs) have been reported to manifest their cytotoxic effects not only in mitosis but also in interphase. However, the relationship between phase-specific susceptibility and MTA concentration, especially with respect to microtubule integrity, remains poorly defined. In addition, whether microtubule stabilizers and destabilizers act similarly or differ in the ability to induce interphase death is unclear. In order to resolve these uncertainties, we report here the results of a systematic comparison of primary acute lymphoblastic leukemia (ALL) and HeLa cells treated with three different MTAs, namely the microtubule stabilizer paclitaxel and two microtubule destabilizers, vincristine, and eribulin...
December 19, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/30576620/tumor-cell-escape-from-therapy-induced-senescence
#15
Tareq Saleh, Liliya Tyutyunyk-Massey, Graeme F Murray, Moureq R Alotaibi, Ajinkya S Kawale, Zeinab Elsayed, Scott C Henderson, Vasily Yakovlev, Lynne W Elmore, Amir Toor, Hisashi Harada, Jason Reed, Joseph W Landry, David A Gewirtz
H460 non-small cell lung, HCT116 colon and 4T1 breast tumor cell lines induced into senescence by exposure to either etoposide or doxorubicin were able to recover proliferative capacity both in mass culture and when enriched for the senescence-like phenotype by flow cytometry (based on β-galactosidase staining and cell size, and a senescence-associated reporter, BTG1-RFP). Recovery was further established using both real-time microscopy and High-Speed Live-Cell Interferometry (HSLCI) and was shown to be accompanied by the attenuation of the senescence-associated secretory phenotype (SASP)...
December 18, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/30566892/rna-interference-screen-identifies-naa10-as-a-regulator-of-pxr-transcription
#16
Peter O Oladimeji, William C Wright, Jing Wu, Taosheng Chen
The pregnane X receptor (PXR) is a principal xenobiotic receptor crucial in the detection, detoxification, and clearance of toxic substances from the body. PXR plays a vital role in the metabolism and disposition of drugs, and elevated PXR levels contribute to cancer drug resistance. Therefore, to modulate PXR activity and mitigate drug resistance, it is imperative to fully understand its regulation. To this end, we screened a transcription factor siRNA library in pancreatic cancer cells that express high levels of PXR...
December 16, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/30557554/inositol-hexakisphosphate-increases-the-size-of-platelet-aggregates
#17
Maria A Brehm, Ulrike Klemm, Christoph Rehbach, Nina Erdmann, Katra Kolšek, Hongying Lin, Camilo Aponte-Santamaría, Frauke Gräter, Bernhard H Rauch, Andrew M Riley, Georg W Mayr, Barry V L Potter, Sabine Windhorst
The inositol phosphates, InsP5 and InsP6 , have recently been identified as binding partners of fibrinogen, which is critically involved in hemostasis by crosslinking activated platelets at sites of vascular injury. Here, we investigated the putative physiological role of this interaction and found that platelets increase their InsP6 concentration upon stimulation with the PLC-activating agonists thrombin, collagen I and ADP and present a fraction of it at the outer plasma membrane. Cone and plate analysis in whole blood revealed that InsP6 specifically increases platelet aggregate size...
December 14, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/30557553/lung-cancer-stem-cells-origin-features-maintenance-mechanisms-and-therapeutic-targeting
#18
REVIEW
Win Sen Heng, Reinoud Gosens, Frank A E Kruyt
Lung cancer remains the leading cause of cancer-related deaths despite recent breakthroughs in immunotherapy. The widely embraced cancer stem cell (CSC) theory has also been applied for lung cancer, postulating that an often small proportion of tumor cells with stem cell properties are responsible for tumor growth, therapeutic resistance and metastasis. The identification of these CSCs and underlying molecular maintenance mechanisms is considered to be absolutely necessary for developing therapies for their riddance, hence achieving remission...
December 14, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/30553787/development-of-a-novel-sensitive-cell-based-corin-assay
#19
Pascal Lambertz, Laura Theisen, Natalie Längst, Colin W Garvie, Bryan T MacDonald, John Yu, Nadine H Elowe, Dmitry Zubov, Virendar K Kaushik, Frank Wunder
Corin (atrial natriuretic peptide-converting enzyme, EC 3.4.21) is a transmembrane serine protease expressed in cardiomyocytes. Corin exerts its cardioprotective effects via the proteolytic cleavage and activation of pro-atrial natriuretic peptide (pro-ANP) to ANP. We recently described an ANP reporter cell line stably expressing the ANP receptor, a cGMP-dependent cation channel used as a real-time cGMP biosensor, and the Ca2+ -sensitive photoprotein aequorin. Here, we describe the generation of a novel reporter cell line expressing the calcium biosensor GCaMP6 instead of aequorin...
December 13, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/30552871/darpp-32-and-t-darpp-protein-products-of-ppp1r1b-old-dogs-with-new-tricks
#20
REVIEW
By Arabo Avanes, Gal Lenz, Jamil Momand
The PPP1R1B gene is located on chromosome 17q12 (39,626,208-39,636,626[GRCh38/hg38]), which codes for multiple transcripts and two experimentally-documented proteins Darpp-32 and t-Darpp. Darpp-32 (Dopamine and cAMP Regulated Phosphoprotein), discovered in the early 1980s, is a protein whose phosphorylation is upregulated in response to cAMP in dopamine-responsive tissues in the brain. It's phosphorylation profile modulates its ability to bind and inhibit Protein Phosphatase 1 activity, which, in turn, controls the activity of hundreds of phosphorylated proteins...
December 12, 2018: Biochemical Pharmacology
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