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Amino Acid And Cancer Cells

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https://read.qxmd.com/read/30772128/design-synthesis-and-biological-evaluation-of-low-molecular-weight-cxcr4-ligands
#1
Maxwell M Sakyiamah, Takuya Kobayakawa, Masayuki Fujino, Makoto Konno, Tetsuo Narumi, Tomohiro Tanaka, Wataru Nomura, Naoki Yamamoto, Tsutomu Murakami, Hirokazu Tamamura
The chemokine receptor CXCR4/stromal cell-derived factor-1 (SDF-1: CXCL12) signaling axis represents a crucial drug target due to its relevance to several diseases such as HIV-1 infection, cancer, leukemia, and rheumatoid arthritis. With the aim of enhancing the binding affinity and anti-HIV activity of a potent CXCR4 ligand as a lead, 23 low molecular weight compounds containing dipicolylamine (Dpa) and cyclam cationic moieties with varying spacers and spatial positioning were designed, synthesized and biologically evaluated...
February 6, 2019: Bioorganic & Medicinal Chemistry
https://read.qxmd.com/read/30770566/design-and-synthesis-of-novel-celastrol-derivative-and-its-antitumor-activity-in-hepatoma-cells-and-antiangiogenic-activity-in-zebrafish
#2
Gang Wang, Qi Xiao, Yao Wu, Ying-Jie Wei, Yue Jing, Xiang-Rong Cao, Zhu-Nan Gong
Two series of celastrol derivatives were designed and synthesized by modifying carboxylic acid at the 28th position with amino acid, and their intermediates with isobutyrate at the third position. All compounds were evaluated for their antiproliferation activity by four human cancer cell lines (SCG7901, HGC27, HepG2, and Bel7402) and one normal cell LO2. The most promising compound, compound 8, showed superior bioactivity and lower toxicity than others including celastrol. Further underlying tests illustrated that compound 8 induced apoptosis and cell arrest at G2/M and inhibited proliferation and mobility of human hepatoma cells by suppressing the signal transducer and activator of transcription-3 signaling pathway...
February 15, 2019: Journal of Cellular Physiology
https://read.qxmd.com/read/30769864/a-h2ax%C3%A2-carp-1-interaction-regulates-apoptosis-signaling-following-dna-damage
#3
Sreeja C Sekhar, Jaganathan Venkatesh, Vino T Cheriyan, Magesh Muthu, Edi Levi, Hadeel Assad, Paul Meister, Vishnu V Undyala, James W Gauld, Arun K Rishi
Cell Cycle and Apoptosis Regulatory Protein (CARP-1/CCAR1) is a peri-nuclear phosphoprotein that regulates apoptosis via chemotherapeutic Adriamycin (doxorubicin) and a novel class of CARP-1 functional mimetic (CFM) compounds. Although Adriamycin causes DNA damage, data from Comet assays revealed that CFM-4.16 also induced DNA damage. Phosphorylation of histone 2AX (γH2AX) protein is involved in regulating DNA damage repair and apoptosis signaling. Adriamycin or CFM-4.16 treatments inhibited cell growth and caused elevated CARP-1 and γH2AX in human breast (HBC) and cervical cancer (HeLa) cells...
February 14, 2019: Cancers
https://read.qxmd.com/read/30768975/sprenylc-pseaac-a-sequence-based-model-developed-via-chou-s-5-steps-rule-and-general-pseaac-for-identifying-s-prenylation-sites-in-proteins
#4
Waqar Hussain, Yaser Daanial Khan, Nouman Rasool, Sher Afzal Khan, Kuo-Chen Chou
The protein prenylation (or S-prenylation) is one of the most essential modifications, required for the association of membrane of a plethora of signalling proteins with the key biological process such as protein trafficking, cell growth, proliferation and differentiation. Due to the ubiquitous nature of S-prenylation and its role in cellular functions, any defect in the biosynthesis or regulation of the isoprenoid leads to the occurrence of a variety of diseases including neurodegenerative disorders, metabolic issues, cardiovascular diseases and one of the most fatal diseases, cancer...
February 12, 2019: Journal of Theoretical Biology
https://read.qxmd.com/read/30765787/oncogenic-y68-frame-shift-mutation-of-pten-represents-a-mechanism-of-docetaxel-resistance-in-endometrial-cancer-cell-lines
#5
Haiyang Zhang, Song Wang, Nicholas Cacalano, He Zhu, Qiuju Liu, Michael Xie, Mitchell Kamrava, Gottfried Konecny, Shunzi Jin
In this study, we aimed to identify mutations of key genes associated with docetaxel resistance in nine endometrial cancer cell lines. Endometrial cancers are associated with several critical gene mutations, including PIK3A, PTEN, and KRAS. Different gene mutations in endometrial cancer cells have varied responses to anticancer drugs and cancer therapies. The most frequently altered gene in endometrioid endometrial carcinoma tumors is PTEN. PTEN protein has lipid phosphatase and protein phosphatase activity, as well as other functions in the nucleus...
February 14, 2019: Scientific Reports
https://read.qxmd.com/read/30763986/suppressor-of-variegation-3-9-homolog-2-a-novel-binding-protein-of-translationally-controlled-tumor-protein-regulates-cancer-cell-proliferation
#6
A-Reum Kim, Jee Young Sung, Seung Bae Rho, Yong-Nyun Kim, Kyungsil Yoon
Suppressor of Variegation 3-9 Homolog 2 (SUV39H2) methylates the lysine 9 residue of histone H3 and induces heterochromatin formation, resulting in transcriptional repression or silencing of target genes. SUV39H1 and SUV39H2 have a role in embryonic development, and SUV39H1 was shown to suppress cell cycle progression associated with Rb. However, the function of human SUV39H2 has not been extensively studied. We observed that forced expression of SUV39H2 decreased cell proliferation by inducing G₁ cell cycle arrest...
February 15, 2019: Biomolecules & Therapeutics
https://read.qxmd.com/read/30763918/effect-of-symmetry-and-metal-nanoparticles-on-the-photophysicochemical-and-photodynamic-therapy-properties-of-cinnamic-acid-zinc-phthalocyanine
#7
Gauta Gold Matlou, Muthumuni Managa, Tebello Nyokong
In this study, a novel asymmetric cinnamic acid zinc phthalocyanine (ZnPc, 1) containing three tert-butyl substituents is reported. The asymmetric ZnPc (1) is further linked to amino functionalized magnetic nanoparticles (AMNPs) (1-AMNPs) and to cysteine functionalized silver nanoparticles (cys-AgNPs) (1-cys-AgNPs) through an amide bond. 1-AMNPs and 1-cys-AgNPs improved the triplet and singlet oxygen quantum yields of complex 1, this was also observed with the previously reported 2-AMNPs when compared to 2 while 3-AMNPs yielded an unexpected decrease in triplet quantum yield as compared to 3...
February 5, 2019: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://read.qxmd.com/read/30761682/novel-specific-human-and-mouse-stromelysin-1-mmp-3-and-stromelysin-2-mmp-10-antibodies-for-biochemical-and-immunohistochemical-analyses
#8
Ursula Mirastschijski, Nilima Dinesh, Sudarson Baskaran, Dirk Wedekind, Jelena Gavrilovic, Megan Y Murray, Damon Bevan, Sørge Kelm
Matrix metalloproteinases (MMP) are a family of more than 25 zinc-dependent enzymes that are centrally involved in cellular migration, tissue remodelling, cancer invasion and metastasis. Besides degrading extracellular matrix proteins, MMPs are crucial for growth factor and cytokine release and activation. At the same time, they can inactivate inflammatory mediators and enzymes themselves through protein degradation. Subclasses of MMPs include collagenases, gelatinases, stromelysins, membrane-bound MMPs and others...
February 14, 2019: Wound Repair and Regeneration
https://read.qxmd.com/read/30761180/intrinsic-fgfr2-and-ectopic-fgfr1-signaling-in-the-prostate-and-prostate-cancer
#9
REVIEW
Cong Wang, Ziying Liu, Yuepeng Ke, Fen Wang
Advanced castrate-resistant prostate cancer (CRPC) is a poorly prognostic disease currently lacking effective cure. Understanding the molecular mechanism that underlies the initiation and progression of CRPC will provide new strategies for treating this deadly disease. One candidate target is the fibroblast growth factor (FGF) signaling axis. Loss of the intrinsic FGF7/FGF10-type 2 FGF receptor (FGFR2) pathway and gain of the ectopic type 1 FGF receptor (FGFR1) pathway are associated with the progression to malignancy in prostate cancer (PCa) and many other epithelial originating lesions...
2019: Frontiers in Genetics
https://read.qxmd.com/read/30755350/structure-activity-relationship-of-leucyladenylate-sulfamate-analogues-as-leucyl-trna-synthetase-lrs-targeting-inhibitors-of-mammalian-target-of-rapamycin-complex-1-mtorc1
#10
Suyoung Yoon, Sung-Eun Kim, Jong Hyun Kim, Ina Yoon, Phuong-Thao Tran, Jihyae Ann, Changhoon Kim, Woong Sub Byun, Sangkook Lee, Sunghoon Kim, Jiyoun Lee, Jeewoo Lee
Leucyl-tRNA synthetase (LRS) plays an important role in amino acid-dependent mTORC1 signaling, which is known to be associated with cellular metabolism and proliferation. Therefore, LRS-targeting small molecules that can suppress mTORC1 activation may provide an alternative strategy to current anticancer therapy. In this work, we developed a library of leucyladenylate sulfate analogues by extensively modifying three different pharmacophoric regions comprising adenine, ribose and leucine. Several effective compounds were identified by cell-based mTORC1 activation assays and further tested for anticancer activity...
January 30, 2019: Bioorganic & Medicinal Chemistry
https://read.qxmd.com/read/30753403/membrane-androgen-receptors-unrelated-to-nuclear-steroid-receptors
#11
Peter Thomas
Rapid (nongenomic) membrane-initiated androgen actions have been described in nuclear androgen (AR) receptor-null cells. Four distinct proteins have been proposed as membrane androgen receptors (mAR) or sensors. TRPM8 is a calcium channel that acts as a pain receptor and mediates androgen- and menthol-induced increases in calcium levels and survival of prostate cancer cells. Testosterone (T) directly interacts with TRPM8, but extensive androgen receptor binding studies to confirm its role as a mAR are lacking...
February 11, 2019: Endocrinology
https://read.qxmd.com/read/30747522/bioinspired-small-molecule-tools-for-the-imaging-of-redox-biology
#12
Amandeep Kaur, Elizabeth J New
The availability of electrons to biological systems underpins the mitochondrial electron transport chain (ETC) that powers living cells. It is little wonder, therefore, that the sufficiency of electron supply is critical to cellular health. Considering mitochondrial redox activity alone, a lack of oxygen (hypoxia) leads to impaired production of adenosine triphosphate (ATP), the major energy currency of the cell, whereas excess oxygen (hyperoxia) is associated with elevated production of reactive oxygen species (ROS) from the interaction of oxygen with electrons that have leaked from the ETC...
February 12, 2019: Accounts of Chemical Research
https://read.qxmd.com/read/30738335/enhancing-magnetic-resonance-photoluminescence-imaging-guided-photodynamic-therapy-by-multiple-pathways
#13
Pei Liu, Jinghua Ren, Yuxuan Xiong, Zhe Yang, Wei Zhu, Qianyuan He, Zushun Xu, Wenshan He, Jing Wang
Mitochondria, which are a major source of adenosine triphosphate (ATP) and apoptosis regulators, are the key organelles that promote tumor cell proliferation, and their dysfunction affects tumor cell behavior. Additionally, mitochondria have been shown to play a central role in the biosynthesis of protoporphyrin IX (PpIX), which is a widely used photosensitizer that has been used for tumor detection, monitoring and photodynamic therapy. Nevertheless, photosensitizers administrated exogenously are often restricted by limited bioavailability...
February 2, 2019: Biomaterials
https://read.qxmd.com/read/30738038/transport-of-cystine-across-xc-antiporter
#14
Maryam Ghasemitarei, Maksudbek Yusupov, Jamoliddin Razzokov, Babak Shokri, Annemie Bogaerts
Extracellular cystine (CYC) uptake by xC- antiporter is important for the cell viability. Especially in cancer cells, the upregulation of xC- activity is observed, which protects these cells from intracellular oxidative stress. Hence, inhibition of the CYC uptake may eventually lead to cancer cell death. Up to now, the molecular level mechanism of the CYC uptake by xC- antiporter has not been studied in detail. In this study, we applied several different simulation techniques to investigate the transport of CYC through xCT, the light subunit of the xC- antiporter, which is responsible for the CYC and glutamate translocation...
February 6, 2019: Archives of Biochemistry and Biophysics
https://read.qxmd.com/read/30736291/novel-targeted-anti-tumor-nanoparticles-developed-from-folic-acid-modified-2-deoxyglucose
#15
Shaoming Jin, Zhongyao Du, Huiyuan Guo, Hao Zhang, Fazheng Ren, Pengjie Wang
The glucose analog, 2-deoxyglucose (2-DG), specifically inhibits glycolysis of cancer cells and interferes with the growth of cancer cells. However, the excellent water solubility of 2-DG makes it difficult to be concentrated in tumor cells. In this study, a targeted nano-pharmacosome was developed with folic acid-modified 2-DG (FA-2-DG) by using amino ethanol as a cleavable linker. FA-2-DG was able to self-assemble, forming nano-particles with diameters of 10⁻30 nm. The biological effects were evaluated with cell viability assays and flow cytometry analysis...
February 6, 2019: International Journal of Molecular Sciences
https://read.qxmd.com/read/30735369/a-metabolic-engineering-approach-to-incorporate-modified-pyrimidine-nucleosides-into-cellular-rna
#16
Yu Zhang, Ralph E Kleiner
The incorporation of chemically modified nucleotides into RNA is a powerful strategy to probe RNA function and has been exploited in the development of anti-cancer and anti-viral drugs. While a wide variety of mod-ified nucleotides can be incorporated into RNA in vitro using chemical or enzymatic synthesis, strategies for the metabolic incorporation of artificial nucleotides into cellular RNA are limited, largely due to the incompati-bility of modified nucleobases and nucleosides with nucleotide salvage pathways...
February 8, 2019: Journal of the American Chemical Society
https://read.qxmd.com/read/30725454/quantitation-of-macropinocytosis-in-cancer-cells
#17
Koen M O Galenkamp, Basheer Alas, Cosimo Commisso
Macropinocytosis has emerged as an important nutrient supply pathway that sustains cell growth of cancer cells within the nutrient-poor tumor microenvironment. By internalizing extracellular fluid through this bulk endocytic pathway, albumin is supplied to the cancer cells, which, after degradation, serves as an amino acid source to meet the high nutrient demands of these highly proliferating cells. Here, we describe a streamlined protocol for visualization and quantitation of macropinosomes in adherent cancer cells grown in vitro...
2019: Methods in Molecular Biology
https://read.qxmd.com/read/30725450/use-of-13-c-3-15-n-1-serine-or-13-c-5-15-n-1-methionine-for-studying-methylation-dynamics-in-cancer-cell-metabolism-and-epigenetics
#18
Alice C Newman, Christiaan F Labuschagne, Karen H Vousden, Oliver D K Maddocks
Tracing the fate of carbon-13 (13 C) labeled metabolites within cells by liquid chromatography mass spectrometry (LCMS) is a powerful analytical technique used for many years in the study of cell metabolism. Conventional experiments using LCMS and labeled nutrients tend to track the incorporation of 13 C from exogenous nutrients (such as amino acids) into other, relatively proximal, cellular metabolites. Several labs have extended this technique to track transfer of 13 C from the metabolite pool onto macromolecules, such as DNA, where methylation acts as an important functional modification...
2019: Methods in Molecular Biology
https://read.qxmd.com/read/30725425/homocysteine-thioretinaco-ozonide-and-oxidative-phosphorylation-in-cancer-and-aging-a-proposed-clinical-trial-protocol
#19
Kilmer S McCully
The objective of the proposed clinical interventional trial is to demonstrate the efficacy of a novel therapeutic strategy in subjects with cancer and hyperhomocysteinemia. Following discovery of abnormal homocysteine thiolactone metabolism in cultured malignant cells, thioretinamide, the amide synthesized from retinoic acid and homocysteine thiolactone, and thioretinaco, the complex formed from cobalamin and thioretinamide, were demonstrated to have antineoplastic, anticarcinogenic, and anti-atherogenic properties in animal models...
2019: Methods in Molecular Biology
https://read.qxmd.com/read/30725408/preclinical-breast-cancer-models-to-investigate-metabolic-priming-by-methionine-restriction
#20
Elena Strekalova, Dmitry Malin, Harisha Rajanala, Vincent L Cryns
We have developed a novel therapeutic paradigm ("metabolic priming") for cancer whereby restriction of the essential amino acid methionine activates a number of cell-stress-response pathways that can be selectively targeted to enhance the therapeutic impact of methionine restriction. One example of metabolic priming is the combination of methionine restriction with proapoptotic TRAIL receptor-2 (TRAIL-R2) agonists. Methionine restriction enhances the cell surface expression of TRAIL-R2 selectively in transformed breast epithelial cells and renders them more susceptible to cell death induction by TRAIL-R2 agonists in cellular and murine models of breast cancer...
2019: Methods in Molecular Biology
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