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Galina A Gazieva, Alexei N Izmest'ev, Lada V Anikina, Sergey A Pukhov, Marina E Meshchaneva, Dmitry V Khakimov, Natalya G Kolotyrkina, Angelina N Kravchenko
A series of tetrahydroimidazo[4,5-e]thiazolo[3,2-b]-1,2,4-triazine-2,7(1H, 6H)-diones were synthesized via the reaction of imidazotriazinethiones and bromoacetic acid followed by condensation with isatins. Amidine skeletal rearrangement of 3,3a,9,9a-tetrahydroimidazo[4,5-e]thiazolo[3,2-b]-1,2,4-triazine-2,7 (1H, 6H)-diones into 1,3a,4,9a-tetrahydroimidazo[4,5-e]thiazolo[2,3-c]-1,2,4-triazine-2,8 (3H, 7H)-diones under KOH treatment has been studied. The influence of substituents at positions 1,3,3a,6,9a of imidazothiazolotriazine on the ability to undergo rearrangement was analyzed based on experimental data and theoretical calculations...
March 14, 2018: Molecular Diversity
Justin Stebbing, Kalpit Shah, Lei Cheng Lit, Teresa Gagliano, Angeliki Ditsiou, Tingting Wang, Franz Wendler, Thomas Simon, Krisztina Sára Szabó, Timothy O'Hanlon, Michael Dean, April Camilla Roslani, Swee Hung Cheah, Soo-Chin Lee, Georgios Giamas
Lemur tyrosine kinase 3 (LMTK3) is an oncogenic kinase that is involved in different types of cancer (breast, lung, gastric, colorectal) and biological processes including proliferation, invasion, migration, chromatin remodeling as well as innate and acquired endocrine resistance. However, the role of LMTK3 in response to cytotoxic chemotherapy has not been investigated thus far. Using both 2D and 3D tissue culture models, we found that overexpression of LMTK3 decreased the sensitivity of breast cancer cell lines to cytotoxic (doxorubicin) treatment...
March 15, 2018: Oncogene
Xiang-Mei Tan, Lu-Ying Li, Li-Yan Sun, Bing-Da Sun, Shu-Bin Niu, Meng-Hua Wang, Xiao-Yan Zhang, Wen-Song Sun, Gui-Shan Zhang, Hui Deng, Xiao-Ke Xing, Zhong-Mei Zou, Gang Ding
Endophytic fungi from desert, arid, and grassland areas are an ecologically important but unique group with poor chemical investigation. During our ongoing study to mine bioactive secondary metabolites from unique fungal environments, a new shunt product spiciferone F (1) including two new analogs spiciferones G (2) and H (3) together with four known ones spiciferone A (4), spiciferol A (5), 6, and 7 were isolated from endophytic fungus Phoma betae inhabiting in plant Kalidium foliatum (Pall.) Moq from Ningxia Province of West China...
March 14, 2018: Journal of Antibiotics
Kumar Parijat Tripathi, Marina Piccirillo, Mario Rosario Guarracino
BACKGROUND: The endomembrane system, known as secretory pathway, is responsible for the synthesis and transport of protein molecules in cells. Therefore, genes involved in the secretory pathway are essential for the cellular development and function. Recent scientific investigations show that ER and Golgi apparatus may provide a convenient drug target for cancer therapy. On the other hand, it is known that abundantly expressed genes in different cellular organelles share interconnected pathways and co-regulate each other activities...
March 8, 2018: BMC Bioinformatics
Wenming Wu, Hanli Ruan
Two new triterpenoids, 24(E)-3α,12α-dihydroxyl-lanost-9(11),24-dien-26-oid acid (1) and 3,4-seco-24(Z)-6α,7β-dihydroxyl-cycloart-4(28),24-dien-3,26-dioic-3-methyl ester (2), and ten known ones (3-12), together with eight lignans (13-20), were isolated from the stems of Schisandra glaucescens. Their structures were established on the basis of extensive spectroscopic analyses. Compounds 1-3, 5-7, 9, 11-13 and 15-18 were isolated from this species for the first time. 1 and 2 were evaluated for their in vitro cytotoxicities against the mouse cancer B16 cell line, human cancer HepG2 and MCF7 cell lines by MTT assay...
March 12, 2018: Natural Product Research
Rafidah Ahmad, I Sahidin, Muhammad Taher, ChenFei Low, Normah Mohd Noor, Chanin Sillapachaiyaporn, Siriporn Chuchawankul, Tewarit Sarachana, Tewin Tencomnao, Faizah Iskandar, Nor Fadilah Rajab, Syarul Nataqain Baharum
Polygonumins A, a new compound, was isolated from the stem of Polygonum minus. Based on NMR results, the compound's structure is identical to that of vanicoside A, comprising four phenylpropanoid ester units and a sucrose unit. The structure differences were located at C-3″″'. The cytotoxic activity of polygonumins A was evaluated on several cancer cell lines by a cell viability assay using tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The compound showed the highest antiproliferative (p < 0...
March 9, 2018: Scientific Reports
Akimitsu Yamada, Masayuki Nagahashi, Tomoyoshi Aoyagi, Wei-Ching Huang, Santiago Lima, Nitai C Hait, Aparna Maiti, Kumiko Kida, Krista P Terracina, Hiroshi Miyazaki, Takashi Ishikawa, Itaru Endo, Michael R Waters, Qianya Qi, Li Yan, Sheldon Milstien, Sarah Spiegel, Kazuaki Takabe
Sphingosine-1-phosphate (S1P), a bioactive sphingolipid mediator, has been implicated in regulation of many processes important for breast cancer progression. Previously we observed that S1P is exported out of human breast cancer cells by ATP-binding cassette (ABC) transporter ABCC1, but not by ABCB1, both known multidrug resistance proteins that efflux chemotherapeutic agents. However, the pathological consequences of these events to breast cancer progression and metastasis has not been elucidated. Here, it is demonstrated that high expression of ABCC1, but not ABCB1, is associated with poor prognosis in breast cancer patients...
March 9, 2018: Molecular Cancer Research: MCR
Srikanth Appikonda, Kaushik N Thakkar, Parantu K Shah, Sharon Y R Dent, Jannik N Andersen, Michelle Craig Barton
Proteins with domains that recognize and bind post-translational modifications (PTMs) of histones are collectively termed epigenetic readers. Numerous interactions between specific reader protein domains and histone PTMs and their regulatory outcomes have been reported, but little is known about how reader proteins may in turn be modulated by these interactions. Tripartite motif-containing protein 24 (TRIM24) is a histone reader aberrantly expressed in multiple cancers. Here, our investigation revealed functional crosstalk between histone acetylation and TRIM24 SUMOylation...
March 9, 2018: Journal of Biological Chemistry
Merve Ertas, Zafer Sahin, Barkin Berk, Leyla Yurttas, Sevde N Biltekin, Seref Demirayak
Drugs used in breast cancer treatments target the suppression of estrogen biosynthesis. During this suppression, the main goal is to inhibit the aromatase enzyme that is responsible for the cyclization and structuring of estrogens either with steroid or non-steroidal-type inhibitors. Non-steroidal derivatives generally have a planar aromatic structure attached to the triazole ring system in their structures, which inhibits hydroxylation reactions during aromatization by coordinating the heme group. Bioisosteric replacement of the triazole ring system and development of aromatic/cyclic structures of the side chain can increase the selectivity for aromatase enzyme inhibition...
March 9, 2018: Archiv der Pharmazie
Fangxu Sun, Alexander A Choi, Ronghu Wu
Fatty acids (FAs) are essential components in cells and are involved in many cellular activities. Abnormal FA metabolism has been reported to be related to human diseases such as cancer and cardiovascular diseases. Identification and quantification of FAs provide insights into their functions in biological systems, but it is very challenging to analyze them due to their structures and properties. In this work, we developed a novel method by integrating tagging FAs with stable isotope labeled aminoxy tandem mass tags (aminoxyTMTs) and mass spectrometric analysis with the positive mode...
March 9, 2018: Journal of Proteome Research
Lauren J Jablonowski, Dolores Conover, Nutte T Teraphongphom, Margaret A Wheatley
This study represents the first attempt to combine surface TRAIL expression and doxorubicin co-encapsulation in a single drug delivery agent in the form of ultrasound-responsive microbubbles that shatter into fragments, or nanoshards, in an ultrasound beam. We compare customized microbubbles of different polymeric shell compositions, and investigate the effect of both shell composition and incorporation of doxorubicin on action against TRAIL-sensitive MDA-MB-231 and TRAIL-resistant MCF7 human breast adenocarcinoma cells...
March 9, 2018: Journal of Biomedical Materials Research. Part A
Nesa Jafari, Sonbol Nazeri, Sattar Tahmasebi Enferadi
BACKGROUND: Use of pharmaceutical agent for breast cancer chemotherapy is an interesting method that induces cells death by different way, such as apoptosis. Parthenolide is the main compound in feverfew that has been used to cure migraine and rheumatoid arthritis for long time. Parthenolide has been predominately investigated as inducer of apoptosis in human cancer cells. PURPOSE: We examined the expression of vimentin and Elongation factor α - 1 as breast cancer biomarkers in MCF7 cells exposure to Parthenolide...
March 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Ahmed Ramadan El-Rokh, Amr Negm, Maha El-Shamy, Mohamed El-Gindy, Mamdouh Abdel-Mogib
Four previously undescribed sucrose diester of aryldihydronaphthalene-type lignans, named echiumins A-D, were isolated from the butanol fraction of Echium angustifolium Mill, in addition to a known compound, trigonotin A, which is reported for the first time from the title plant. The structures of isolated compounds were elucidated using spectroscopic methods such as HRESIMS and 1D and 2D NMR spectroscopy. The isolated compounds displayed strong to weak antitumor activity against HepG2 and MCF7 cancer cell lines, with echiumins A and D showed the most potent activity...
March 5, 2018: Phytochemistry
Fatemeh Safa Shams Abyaneh, Mahboube Eslami Moghadam, Adeleh Divsalar, Davood Ajloo, Moyaed Hosaini Sadr
Methylglycine, also known sarcosine, is dramatically used in drug molecules and its metal complexes can interact to DNA and also do cleavage. Hence, to study the influence of methylglycine ligand on biological behavior of metal complexes, two water-soluble platinum (II) complexes with the formula cis-[Pt(NH3 )2 (CH3 -gly)]NO3 and cis-[Pt(NH2 -CH3 )2 (CH3 -gly)]NO3 (where CH3 -gly is methylglycine) have been synthesized and characterized by spectroscopic methods, molar conductivity measurements, and elemental analyzes...
March 8, 2018: Applied Biochemistry and Biotechnology
Liga Saulite, Karlis Pleiko, Ineta Popena, Dominyka Dapkute, Ricardas Rotomskis, Una Riekstina
We created a 3D cell co-culture model by combining nanoengineered mesenchymal stem cells (MSCs) with the metastatic breast cancer cell line MDA-MD-231 and primary breast cancer cell line MCF7 to explore the transfer of quantum dots (QDs) to cancer cells. First, the optimal conditions for high-content QD loading in MSCs were established. Then, QD uptake in breast cancer cells was assessed after 24 h in a 3D co-culture with nanoengineered MSCs. We found that incubation of MSCs with QDs in a serum-free medium provided the best accumulation results...
2018: Beilstein Journal of Nanotechnology
Sabrin R M Ibrahim, Hossam M Abdallah, Ali M El-Halawany, Alaa M Nafady, Gamal A Mohamed
A new prenylated xanthone, mangostanaxanthone VIII (7) and six known metabolites: gartanin (1), 1,3,8-trihydroxy-2-(3-methyl-2-butenyl)-4-(3-hydroxy-3-methylbutanoyl)-xanthone (2), rubraxanthone (3), 1,3,6,7-tetrahydroxy-8-prenylxanthone (4), garcinone C (5), and xanthone I (9-hydroxycalabaxanthone) (6) were separated from the EtOAc-soluble fraction of the air-dried pericarps of Garcinia mangostana (Clusiaceae). Their structures have been verified on the basis of spectroscopic data analysis as well as comparison with the literature...
March 7, 2018: Natural Product Research
Yunhee Cho, Hyeok Gu Kang, Seok-Jun Kim, Seul Lee, Sujin Jee, Sung Gwe Ahn, Min Jueng Kang, Joon Seon Song, Joon-Yong Chung, Eugene C Yi, Kyung-Hee Chun
Recurrence and drug resistance of breast cancer are still the main reasons for breast cancer-associated deaths. Cancer stem cell (CSC) model has been proposed as a hypothesis for the lethality of breast cancer. Molecular mechanisms underlying CSC maintenance are still unclear. In this study, we generated mammospheres derived from breast cancer MDA-MB231 cells and MCF7 cells to enrich CSCs and performed DNA microarray analysis. We found that the expression of carboxy terminus of HSP70-interacting protein (CHIP) E3 ubiquitin ligase was significantly downregulated in breast CSCs...
March 6, 2018: Cell Death and Differentiation
Hoon Kim, Qun Lin, Peter M Glazer, Zhong Yun
BACKGROUND: Tumor hypoxia is an independent prognostic factor associated with poor patient survival. Emerging evidence suggests that hypoxia can potentially maintain or enhance the stem cell phenotype of both normal stem cells and cancer cells. However, it remains to be determined whether cell fate is regulated in vivo by the hypoxic tumor microenvironment (TME). METHODS: We established a hypoxia-sensing xenograft model to identify hypoxic tumor cell in vivo primarily using human breast cancer cell lines MDA-MB-231 and MCF7...
March 6, 2018: Breast Cancer Research: BCR
Yanmei Zou, Yuandong Chen, Shuo Yao, Guangrui Deng, Dian Liu, Xun Yuan, Shunfang Liu, Jie Rao, Huihua Xiong, Xianglin Yuan, Shiying Yu, Feng Zhu, Yihua Wang, Hua Xiong
OBJECTIVE: This study investigated miR-422a and PLP2 expressions in breast cancer cells and breast cancer stem cells (BCSCs). Besides, their influences on polymorphism changes were observed. METHODS: Flow cytometry and fluorescence-activated cell sorting was performed and CD24- /CD44+ cells were sorted from breast cancer cells and recognized as BCSCs. Microarray was applied to search for the differentially expressed miRNAs and mRNAs between MCF7 and BCSCs. The aberrant expression of miR-422a and PLP2 was further confirmed by RT-qPCR and the direct targeted relationship was verified by dual-luciferase reporter assay...
March 6, 2018: Cancer Biology & Therapy
Svetlana V Vasilyeva, Inga R Grin, Boris P Chelobanov, Dmitry A Stetsenko
A conjugate of triphosphorylated 2',3'-dideoxyuridine (ddU) with SiO2 nanoparticles was obtained via the CuAAC click chemistry between a γ-alkynyl ddU triphosphate and azido-modified SiO2 nanoparticles. Assessment of cytotoxicity in human breast adenocarcinoma MCF7 cells demonstrated that ddU triphosphate conjugated to SiO2 nanoparticles exhibited a 50% decrease in cancer cell growth at a concentration of 183 ± 57 µg/mL, which corresponds to 22 ± 7 µM of the parent nucleotide, whereas the parent nucleoside, nucleotide and alkynyl triphosphate precursor do not show any cytotoxicity...
February 7, 2018: Bioorganic & Medicinal Chemistry Letters
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