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Amino Acid And Cancer Cells

Chen Xu, Ri-Jin Song, Pei Lu, Jian-Chun Chen, Yong-Qiang Zhou, Gang Shen, Min-Jun Jiang, Wei Zhang
Aim: To significantly promote cancer cell uptake and to achieve combination therapy and on-demand drug release, a pH-triggered charge-switchable and redox-responsive drug-release nanovehicle was developed in this study. Materials and methods: The nanocarrier was constructed by conjugating 3,3'-dithiodipropionic acid-modified doxorubicin (DTPA-DOX) and 2,3-dimethylmaleic anhydride (DMA) to the side amino groups of poly(ethylene glycol)- b -poly(L-lysine) (PEG- b -PLL) and by encapsulating triptolide (TRI) into the hydrophobic core...
2018: International Journal of Nanomedicine
Davide Zella, Sabrina Curreli, Francesca Benedetti, Selvi Krishnan, Fiorenza Cocchi, Olga S Latinovic, Frank Denaro, Fabio Romerio, Muhammad Djavani, Man E Charurat, Joseph L Bryant, Hervé Tettelin, Robert C Gallo
We isolated a strain of human mycoplasma that promotes lymphomagenesis in SCID mice, pointing to a p53-dependent mechanism similar to lymphomagenesis in uninfected p53-/- SCID mice. Additionally, mycoplasma infection in vitro reduces p53 activity. Immunoprecipitation of p53 in mycoplasma-infected cells identified several mycoplasma proteins, including DnaK, a member of the Hsp70 chaperon family. We focused on DnaK because of its ability to interact with proteins. We demonstrate that mycoplasma DnaK interacts with and reduces the activities of human proteins involved in critical cellular pathways, including DNA-PK and PARP1, which are required for efficient DNA repair, and binds to USP10 (a key p53 regulator), impairing p53-dependent anticancer functions...
December 3, 2018: Proceedings of the National Academy of Sciences of the United States of America
Rachel A Battaglia, Samed Delic, Harald Herrmann, Natasha T Snider
The vimentin gene ( VIM ) encodes one of the 71 human intermediate filament (IF) proteins, which are the building blocks of highly ordered, dynamic, and cell type-specific fiber networks. Vimentin is a multi-functional 466 amino acid protein with a high degree of evolutionary conservation among vertebrates. Vim -/- mice, though viable, exhibit systemic defects related to development and wound repair, which may have implications for understanding human disease pathogenesis. Vimentin IFs are required for the plasticity of mesenchymal cells under normal physiological conditions and for the migration of cancer cells that have undergone epithelial-mesenchymal transition...
2018: F1000Research
Erika Rocha-Del Castillo, Omar Gómez-García, Dulce Andrade-Pavón, Lourdes Villa-Tanaca, Teresa Ramírez-Apan, Antonio Nieto-Camacho, Elizabeth Gómez
A series of organotin(IV) complexes was herein prepared and characterized. A one-pot synthetic strategy afforded reasonable to high yields, depending on the nature of the ligand. All new complexes were fully characterized by spectroscopic techniques, consisting of IR, MS and NMR (1 H, 13 C and 119 Sn). The in vitro cytotoxicity tests demonstrated that the organotin complexes produced a greater inhibition, versus cisplatin (the positive control), of the growth of six human cancer cell lines: U-251 (glioblastoma), K-562 (chronic myelogenous leukemia), HCT-15 (colorectal), MCF-7 (breast), MDA-MB-231 (breast) and SKLU-1 (non-small cell lung)...
2018: Chemical & Pharmaceutical Bulletin
Ning-Ning Guo, Xue-Jun Sun, Ya-Kai Xie, Gui-Wen Yang, Cui-Jie Kang
As an important disulfide reductase of the intracellular antioxidant system, Thioredoxin (Trx)plays an important role in maintaining oxidative stress balance and protecting cells from oxidative damage. In recent years, there is increasing evidence that Trx is a key molecule in the pathogenesis of various diseases and a potential therapeutic target for major diseases including lung, colon, cervical, gastric and pancreatic cancer. However, few knowledge is known about the function of Trx in virus infection. In this study, we reported the cloning and functional investigation of a Trx homologue gene, named MjTrx, in shrimp Marsupenaeus japonicus suffered white spot syndrome virus(WSSV) infection...
November 28, 2018: Fish & Shellfish Immunology
Robert Roskoski
The EGFR family is among the most investigated receptor protein-tyrosine kinase groups owing to its general role in signal transduction and in oncogenesis. This family consists of four members that belong to the ErbB lineage of proteins (ErbB1-4). The ErbB proteins function as homo and heterodimers. These receptors contain an extracellular domain that consists of four parts: domains I and III are leucine-rich segments that participate in growth factor binding (except for ErbB2) and domains II and IV contain multiple disulfide bonds...
November 27, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Svetlana N Kovalchuk, Nina S Buinovskaya, Galina N Likhatskaya, Valery A Rasskazov, Oksana M Son, Liudmila A Tekutyeva, Larissa A Balabanova
The GalNAc/Gal-specific lectin from the sea mussel Crenomytilus grayanus (CGL) with anticancer activity represents а novel lectin family with β-trefoil fold. Earlier, the crystal structures of CGL complexes with globotriose, galactose and galactosamine, and mutagenesis studies have revealed that the lectin contained three carbohydrate-binding sites. The ability of CGL to recognize globotriose (Gb3) on the surface of breast cancer cells and bind mucin-type glycoproteins, which are often associated with oncogenic transformation, makes this compound to be perspective as a biosensor for cancer diagnostics...
November 27, 2018: Marine Drugs
Mariana B Marggraf, Pavel V Panteleev, Anna A Emelianova, Maxim I Sorokin, Ilia A Bolosov, Anton A Buzdin, Denis V Kuzmin, Tatiana V Ovchinnikova
Biological activity of the new antimicrobial peptide polyphemusin III from the horseshoe crab Limulus polyphemus was examined against bacterial strains and human cancer, transformed, and normal cell cultures. Polyphemusin III has the amino acid sequence RRGCFRVCYRGFCFQRCR and is homologous to other β-hairpin peptides from the horseshoe crab. Antimicrobial activity of the peptide was evaluated and MIC (minimal inhibitory concentration) values were determined. IC50 (half-maximal inhibitory concentration) values measured toward human cells revealed that polyphemusin III showed a potent cytotoxic activity at concentrations of <10 μM...
November 26, 2018: Marine Drugs
Joana Marquez, Irina Kratchmarova, Vyacheslav Akimov, Fernando Unda, Gaskon Ibarretxe, Ariane Schaub Clerigué, Nerea Osinalde, Iker Badiola
Colon cancer is one of the most frequently occurring types of cancers in the world. Primary tumours are treated very efficiently, but the metastatic cases are known to have severe outcomes. Therefore, the aim of the present study was to obtain a greater understanding of the transformation of primary colon cancer cells into metastatic phenotypes. Small changes in protein expression provoke the metastatic phenotype transformation. More sensitive methods to detect small variations are required. A murine colon cancer cell line with metastatic characteristics in a very early phase was created in order to investigate the first steps of transformation using a murine liver metastasis model...
November 27, 2018: Oncology Reports
Song Zhu, Jizhong Wang, Yutian He, Nan Meng, Guang-Rong Yan
Non-coding RNAs (ncRNAs) are defined as RNA molecules that do not encode proteins, but recent evidence has proven that peptides/proteins encoded by ncRNAs do indeed exist and usually contain less than 100 amino acids. These peptides/proteins play an important role in regulating tumor energy metabolism, epithelial to mesenchymal transition of cancer cells, the stability of the c-Myc oncoprotein, and the ubiquitination and degradation of proliferating cell nuclear antigen (PCNA). These peptides/proteins represent promising drug targets for fighting against tumor growth or biomarkers for predicting the prognosis of cancer patients...
2018: Frontiers in Pharmacology
Soham Mukherjee, Kapil Ganorkar, Ajay Kumar, Naina Sehra, Sujit Kumar Ghosh
Human serum albumin is perceived to be the most abundant protein in human blood plasma and functions as a major carrier of different enzymes and drugs inside human body. The present article puts in an effort to demonstrate the attitude adopted by human serum albumin towards a potential therapeutic luminophore 4-(2-Hydroxyethyl)-10-phenyl-3,4,6,7,8,10-hexahydro-1H-cyclopenta[g]furo[3,4-b]quinoline-1-one (HPFQ). HPFQ is a prodigy from azapodophyllotoxin class of compounds, which have been synthesized from the perspective of improved bioactivity than its prologue podophyllotoxins...
November 16, 2018: Bioorganic Chemistry
Yiwei Wu, Qiuyue Wang, Tingting Wu, Wei Liu, Hexin Nan, Shenghao Xu, Yizhong Shen
The simple, sensitive and specific detection of hydrogen sulfide (H2S) is of great importance due to its crucial role in food safety, environmental pollution, and various pathological and physiological processes. Here, we reported an activatable fluorescence nanoprobe-based quantum dots (QDs) for sensitive and selective monitoring of H2S in red wine, environmental water samples, and lysosome of live cancer cells. The nanoprobe was prepared through a strong electrostatic interaction between thioglycolic acid stabilized CdTe QDs and p-amino thiophenol capped silver nanoparticles (AgNPs) that resulted in the formation of the assembled nanostructure, called QDs/AgNPs nanocomplexes...
November 27, 2018: ACS Applied Materials & Interfaces
Vunnam Srinivasulu, Paul Schilf, Saleh Ibrahim, Monther A Khanfar, Scott McN Sieburth, Hany Omar, Anusha Sebastian, Raed A AlQawasmeh, Matthew John O'Connor, Taleb H Al-Tel
Octahydroindolo[2,3-a]quinolizine ring system forms the basic framework comprised of more than 2000 distinct family members of natural products. Despite the potential applications of this privileged substructure in drug discovery, efficient, atom-economic and modular strategies for its assembly, is underdeveloped. Here we show a one-step build/couple/pair strategy that uniquely allows access to diverse octahydroindolo[2,3-a]quinolizine scaffolds with more than three contiguous chiral centers and broad distribution of molecular shapes via desymmetrization of the oxidative-dearomatization products of phenols...
November 26, 2018: Nature Communications
Mei-Jung Lai, Ritu Ojha, Mei-Hsiang Lin, Yi-Min Liu, Hsueh-Yun Lee, Tony Eight Lin, Kai-Cheng Hsu, Chi-Yen Chang, Mei-Chuan Chen, Kunal Nepali, Jang-Yang Chang, Jing-Ping Liou
We report structure-activity relationships of 1-arylsulfonyl indoline based benzamides. The benzamide (9) exhibits striking tubulin inhibition with an IC50 value of 1.1 μM, better than that of combretastain A-4 (3), and substantial antiproliferative activity against a variety of cancer cells, including MDR-positive cell lines with an IC50 value of 49 nM (KB), 79 nM (A549), 63 nM (MKN45), 64 nM (KB-VIN10), 43 nM (KB-S15), and 46 nM (KB-7D). Dual inhibitory potential of compound 9 was found as it demonstrated significant inhibitory potential against HDAC1, 2 and 6 in comparison to MS-275 (6)...
November 3, 2018: European Journal of Medicinal Chemistry
Fuyun Guo, Shufen Zhao, Xiao'e Li
Pyruvate dehydrogenase kinases (PDKs) are widely over-expressed in various human solid cancers, making them attractive therapeutic targets for cancer treatment. Herein, we report the identification of structurally novel PDKs inhibitors by screening of an in-house small molecule library. Biochemical assay indicated that the identified compounds 1-4 inhibited PDK1 activity with EC50 values of 0.50, 1.99, 4.64, and 0.42 µM, respectively. The ITC analysis suggested that the identified compounds 1-4 were pan-isoform PDK inhibitors, which bound to and inhibited the four PDK isoforms...
November 17, 2018: Bioorganic & Medicinal Chemistry Letters
Tingting Li, Ying Zhu, Fan Cheng, Chu Lu, Jae U Jung, Shou-Jiang Gao
Cancer cells are required to rewire existing metabolic pathways to support their abnormal proliferation. We have previously shown that, unlike glucose-addicted cancers, Kaposi's sarcoma-associated herpesvirus (KSHV)-transformed cells depend on glutamine rather than glucose for energy production, and amino acid and nucleotide syntheses. High-level consumption of glutamine is tightly regulated and often coupled with the citrulline-nitric oxide (NO) cycle. We have found that KSHV infection accelerates the nitrogen efflux by upregulating the expression of argininosuccinate synthase 1 ( ASS1 ), a key enzyme in the citrulline-NO cycle...
November 21, 2018: Journal of Virology
Gennaro Riccio, Eduardo Sommella, Nadia Badolati, Emanuela Salviati, Sara Bottone, Pietro Campiglia, Monica Dentice, Gian Carlo Tenore, Mariano Stornaiuolo, Ettore Novellino
Chemotherapy-induced alopecia (CIA) is a common side effect of conventional chemotherapy and represents a major problem in clinical oncology. Even months after the end of chemotherapy, many cancer patients complain of hair loss, a condition that is psychologically difficult to manage. CIA disturbs social and sexual interactions and causes anxiety and depression. Synthetic drugs protecting from CIA and endowed with hair growth stimulatory properties are prescribed with caution by oncologists. Hormones, growth factors, morphogens could unwontedly protect tumour cells or induce cancer cell proliferation and are thus considered incompatible with many chemotherapy regimens...
November 20, 2018: Nutrients
Seon-Hyeong Lee, Won-Kyu Lee, Nayeon Kim, Joon Hee Kang, Kyung-Hee Kim, Seul-Gi Kim, Jae-Seon Lee, Soohyun Lee, Jongkook Lee, Jungnam Joo, Woo Sun Kwon, Sun Young Rha, Soo-Youl Kim
In general, expression of transglutaminase 2 (TGase 2) is upregulated in renal cell carcinoma (RCC), resulting in p53 instability. Previous studies show that TGase 2 binds to p53 and transports it to the autophagosome. Knockdown or inhibition of TGase 2 in RCC induces p53-mediated apoptosis. Here, we screened a chemical library for TGase 2 inhibitors and identified streptonigrin as a potential therapeutic compound for RCC. Surface plasmon resonance and mass spectroscopy were used to measure streptonigrin binding to TGase 2...
November 19, 2018: Cancers
Elie Hatem, Sandy Azzi, Nadine El Banna, Tiantian He, Amélie Heneman-Masurel, Laurence Vernis, Dorothée Baïlle, Vanessa Masson, Florent Dingli, Damarys Loew, Bruno Azzarone, Pierre Eid, Giuseppe Baldacci, Meng-Er Huang
Background: Cancer cells from different origins exhibit various basal redox statuses and thus respond differently to intrinsic or extrinsic oxidative stress. These intricate characteristics condition the success of redox-based anticancer therapies that capitalize on the ability of reactive oxygen species to achieve selective and efficient cancer cell killing. Methods: Redox biology methods, stable isotope labeling by amino acids in cell culture (SILAC)-based proteomics, and bioinformatics pattern comparisons were used to decipher the underlying mechanisms for differential response of lung and breast cancer cell models to redox-modulating molecule auranofin (AUF) and to combinations of AUF and vitamin C (VC)...
November 20, 2018: Journal of the National Cancer Institute
Silvia Carboni, Antonio Zucca, Sergio Stoccoro, Laura Maiore, Massimiliano Arca, Fabrizio Ortu, Christian Artner, Bernhard K Keppler, Samuel M Meier-Menches, Angela Casini, Maria Agostina Cinellu
A series of novel (C∧ N∧ N) cyclometalated AuIII complexes of general formula [Au(bipydmb -H)X][PF6 ] (bipydmb -H = C∧ N∧ N cyclometalated 6-(1,1-dimethylbenzyl)-2,2'-bipyridine) were prepared with a range of anionic ligands X in the fourth coordination position, featuring C (alkynyl)-, N-, O-, or S-donor atoms. The X ligands are varied in nature and include three coumarins, 4-ethynylaniline, saccharine, and thio-β-d-glucose tetraacetate, the tripeptide glutathione (GSH), and a coumarin-substituted amide derived from 4-ethynylaniline...
November 20, 2018: Inorganic Chemistry
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