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Hongjian Wang, Hui Li, Lei Zhang, Desheng Yang
The existence of drug resistance is the main reason for chemotherapeutic failure in malignancies. Long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) is implicated with tumorigenesis and chemoresistance. In the present study, we aimed to identify the role of MEG3 in oxaliplatin-resistant colorectal cancer (CRC) and its potential mechanisms. MEG3 was down-regulated in oxaliplatin-resistant CRC tissues and cell lines. Low MEG3 expression was correlated with poor prognosis of CRC patients. Overexpression of MEG3 improved oxaliplatin sensitivity of HT29/OXA and HCT116/OXA cells...
July 27, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Yuanyuan Shang, Fang Zhang, Dehui Li, Chang Li, Hongbo Li, Yingjian Jiang, Dianliang Zhang
Ubiquinol-cytochrome c reductase complex core protein 2 (UQCRC2) is an important subunit of mitochondrial respiratory complex III. However, its role in tumorigenesis and tumor progression remains unknown, especially with regards to colorectal cancer (CRC). In this research, we measured the expression of UQCRC2 protein by immunohistochemistry assay in 89 paired paraffin-embedded tumor tissues and corresponding adjacent normal tissues from patients with colorectal adenocarcinoma and investigated possible correlations of UQCRC2 expression with clinicopathological parameters and prognosis...
August 11, 2018: Pathology, Research and Practice
Shunsuke Ito, Miyako Shiraishi, Kazuki Tsuchihashi, Reine Takatsuka, Junpei Yamamoto, Isao Kuraoka, Shigenori Iwai
Mismatched base pairs, produced by nucleotide misincorporation by DNA polymerase, are repaired by the mismatch repair (MMR) pathway to maintain genetic integrity. We have developed a method for the fluorescence detection of the cellular MMR ability. A mismatch, which would generate a stop codon in the mRNA transcript unless it was repaired, was introduced into the gene encoding the enhanced green fluorescent protein (EGFP) in an expression plasmid. When MMR-proficient HeLa cells were transformed with this plasmid, the production of active EGFP was observed by fluorescence microscopy...
August 15, 2018: Scientific Reports
Xichuan Tang, Liwei Tan, Kun Shi, Jinrong Peng, Yao Xiao, Wenting Li, Lijuan Chen, Qian Yang, Zhiyong Qian
Enhancing the heat-sensitivity of tumor cells provides an alternative solution to maintaining the therapeutic outcome of photothermal therapy (PTT). In this study, we constructed a therapeutic system, which was composed of methoxy-polyethylene-glycol-coated-gold-nanorods (MPEG-AuNR) and VER-155008-micelles, to evaluate the effect of VER-155008 on the sensitivity of tumor cells to heat, and further investigate the therapeutic outcome of MPEG-AuNR mediated PTT combined with VER-155008- micelles. VER-155008- micelles down-regulate the expression of heat shock proteins and attenuate the heat-resistance of tumor cell...
July 2018: Acta Pharmaceutica Sinica. B
Nazan Inceler, Yesim Ozkan, Nilufer Nermin Turan, Deniz Cansen Kahraman, Rengul Cetin-Atalay, Sultan Nacak Baytas
With the aim of achieving new compounds possessing both anti-inflammatory and antiplatelet activities, we synthesized ( E )-3-[3-(pyridin-3/4-yl)-1-(phenyl/sulfonylmethylphenyl)-1 H -pyrazol-4-yl]acrylamides, and evaluated their COX-1 and COX-2 inhibitory and antiplatelet activities. Since COX-2 inhibitory and antiplatelet compounds have anticancer potential, we also screened their antiproliferative effects against three human cancer cell lines. Compounds 5n , 5p , 5s , 10d , 10g and 10i were determined as dual COX-2 inhibitor/antiplatelet compounds...
May 1, 2018: MedChemComm
Xianling Ning, Yunqiao Li, Hailong Qi, Ridong Li, Yan Jin, Junyi Liu, Yuxin Yin
Tumor cells reprogram their cellular metabolism by switching from oxidative phosphorylation to aerobic glycolysis to support aberrant cell proliferation. Suppressing tumor cell metabolism has become an attractive strategy for treating cancer patients. In this study, we identified a 2,3-didithiocarbamate-substituted naphthoquinone 3i that inhibited the proliferation of tumor cells by disturbing their metabolism. Compound 3i reduced cancer cell viability with IC50 values from 50 nM to 150 nM against HCT116, MCF7, MDA-MB231, HeLa, H1299 and B16 cells...
April 1, 2018: MedChemComm
Jiyong Hu, Chunli Liao, Ruina Mao, Junshuai Zhang, Jin'an Zhao, Zhenzhen Gu
Copper is an essential element and has redox potential, thus copper complexes have been developed rapidly with the hope of curing cancer. To further develop anticancer agents and investigate their anticancer mechanisms, two Cu complexes, [Cu(bpbb)0.5 ·Cl·SCN]·(CH3 OH) ( 1 ) and [Cu2 (bpbb)·Br3 ·(OH)] n ( 2 ), were synthesized and characterized using 4,4'-bis((2-(pyridin-2-yl)-1 H -benzo[ d ]imidazol-1-yl)methyl)biphenyl (bpbb), with associated Cu(ii) salts. Complex 1 is a binuclear structure, whereas 2 is a one-dimensional complex...
February 1, 2018: MedChemComm
Yonggang Ren, Jia Tao, Zhen Jiang, Dongmei Guo, Jiancai Tang
OBJECTIVE: Wnt/β‑catenin signaling pathway plays important role in colorectal cancer (CRC) and acts as a potential therapeutic target. Pimozide is a FDA-approved clinical drug used to treat psychotic diseases and it has shown anticancer effect in some tumors partially via inhibition of Wnt/β‑catenin signaling pathway. This study aimed to investigate whether pimozide exerts anticancer effect on CRC and explore underlying mechanism. METHODS AND RESULTS: Pimozide was administrated to treat HCT116 and SW480 cells...
August 11, 2018: Life Sciences
Jinsong Wu, Runyuan Zhao, Jing Lin, Baohua Liu
Integrin contributes to the maintenance of cell adhesion. In turn, cell adhesion triggers certain integrin signaling cascades, and influences cell biological behavior. In the present study, we explored the role and mechanism of integrin β4 in the DNA damage response in colorectal cancer (CRC) using a three‑dimensional (3D) cell culture model. Under 3D culture condition, dispersed CRC cells automatically formed multicellular spheroids, which consisted of layers of cells with cell junctions commonly distributed...
October 2018: Oncology Reports
Na Zhou, Zhao Sun, Ningning Li, Yuping Ge, Jianfeng Zhou, Qin Han, Lin Zhao, Chunmei Bai
The incidence and mortality of colorectal cancer (CRC) have been rising rapidly in China. A number of miRNAs have been confirmed to be involved in diverse biological processes of CRC. However, whether miR‑197 plays a role in migration and invasion of CRC has never been explored. In the present study Transwell chambers were used in in vitro migration and invasion assays. Dual-luciferase reporter assay was employed to confirm the target of miR‑197. RT‑PCR and IHC staining were performed to quantify miR‑197 and IGFBP3 expression, respectively...
August 10, 2018: Oncology Reports
Samuel M Meier-Menches, Katja Zappe, Andrea Bileck, Dominique Kreutz, Ammar Tahir, Margit Cichna-Markl, Christopher Gerner
Activation kinetics of metallo-prodrugs control the types of possible interactions with biomolecules. The intact metallo-prodrug is able to engage with potential targets by purely non-covalent bonding, while the activated metallodrug can form additional coordination bonds. It is hypothesized that the additional coordinative bonding might be favourable with respect to the target selectivity of activated metallodrugs. Thus, a time-dependent shotgun proteomics study was conducted in HCT116 colon carcinoma cells with plecstatins, which are organoruthenium anticancer drug candidates...
August 14, 2018: Metallomics: Integrated Biometal Science
Magdalena Szaryńska, Agata Olejniczak, Jarosław Kobiela, Dariusz Łaski, Zbigniew Śledziński, Zbigniew Kmieć
The therapy of colorectal cancer (CRC) patients is often unsuccessful because of the presence of cancer stem cells (CSCs) resistant to conventional approaches. Dendritic cells (DC)-based protocols are believed to effectively supplement CRC therapy. Our study was aimed to assess how the number and properties of CSCs isolated from tumor tissue of CRC patients will affect the biological characteristics of in vitro modified DCs. Similar procedures were conducted with the using of CRC HCT116 and HT29 cell lines...
August 13, 2018: Scientific Reports
Hye-Jun Ham, Jeong-Woo Park, Young-Seuk Bae
We investigated whether SIRT1 is associated with reactive oxygen species (ROS) accumulation during CK2 downregulation-mediated senescence. SIRT1 overexpression suppressed ROS accumulation, reduced transcription of FoxO3a target genes, and nuclear export and acetylation of FoxO3a, which were induced by CK2 downregulation in HCT116 and MCF-7 cells. Conversely, overexpression of a dominant-negative mutant SIRT1 (H363Y) counteracted decreased ROS levels, increased transcriptional activity of FoxO3a, and increased nuclear import and decreased acetylation of FoxO3a, which were induced by CK2 upregulation...
August 14, 2018: BMB Reports
Oluwaseun Adebayo Bamodu, Ching-Kuo Yang, Wei-Hong Cheng, David T W Tzeng, Kuang-Tai Kuo, Chun-Chih Huang, Li Deng, Michael Hsiao, Wei-Hwa Lee, Chi-Tai Yeh
BACKGROUND: Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality in both sexes globally. This is not unconnected with the heterogeneity and plasticity of CRC stem cells (CRC-SCs) which stealthily exploit the niche-related and (epi)genetic factors to facilitate metastasis, chemoresistance, tumor recurrence, and disease progression. Despite the accumulating evidence of the role of dysregulated microRNAs in malignancies, the therapeutic efficacy of pharmacological-targeting of CRC-SC-associated microRNAs is relatively under-explored...
August 10, 2018: Cancers
Bartolomeo Bosco, Andrea Defant, Andrea Messina, Tania Incitti, Denise Sighel, Angela Bozza, Yari Ciribilli, Alberto Inga, Simona Casarosa, Ines Mancini
Reversine is a potent antitumor 2,6-diamino-substituted purine acting as an Aurora kinases inhibitor and interfering with cancer cell cycle progression. In this study we describe three reversine-related molecules, designed by docking calculation, that present structural modifications in the diamino units at positions 2 and 6. We investigated the conformations of the most stable prototropic tautomers of one of these molecules, the N 6-cyclohexyl- N 6-methyl- N 2-phenyl-7 H -purine-2,6-diamine ( 3 ), by Density Functional Theory (DFT) calculation in the gas phase, water and chloroform, the last solvent considered to give insights into the detection of broad signals in NMR analysis...
August 10, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Min Hu, Lisheng Liu, Weirong Yao
Colorectal cancer is a leading cause of cancer-related death. Glutaminolysis has been suggested as a therapeutic target for cancer. Costunolide is a natural sesquiterpene lactone showing potent antitumor activity. Our studies were aimed at evaluating how costunolide affected glutaminolysis leading to proliferation inhibition in human colorectal cancer cells. Costunolide suppressed viability and proliferation of HCT116 cells concentration-dependently, but did not apparently affect human intestinal epithelial cells...
August 10, 2018: Gene
Souad A El-Metwally, Ali K Khalil, Abeer M El-Naggar, Wael M El-Sayed
ackground: Developing new chemotherapeutic agents with molecular targets, larger margin of safety against normal cells and low cost is the target many scientists try to achieve. OBJECTIVE: The present study was undertaken to investigate the anticancer activity of a novel series of thiophene compounds and the molecular mechanisms associated. METHODS: A series of novel heterocyclic compounds including pyrimidine derivatives (2, 3, 4, 5 8, 11, 12, 13, 14, and 15), thiophene derivatives (6, 7, and 10) and oxoisothiazolidine derivative (9) was synthesized from 4,5,6,7-tetrahydrobenzo[b] thiophene (1)...
August 13, 2018: Anti-cancer Agents in Medicinal Chemistry
Saloni Kakkar, Sumit Tahlan, Siong Meng Lim, Kalavathy Ramasamy, Vasudevan Mani, Syed Adnan Ali Shah, Balasubramanian Narasimhan
BACKGROUND: A new series of benzoxazole analogues was synthesized and checked for their in vitro antibacterial, antifungal and anticancer activities. RESULTS AND DISCUSSION: The synthesized benzoxazole compounds were confirmed by IR, 1 H/13 C-NMR, mass and screened for their in vitro antimicrobial activity against Gram-positive bacterium: Bacillus subtilis, four Gram-negative bacteria: Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi and two fungal strains: Candida albicans and Aspergillus niger using tube dilution technique and minimum inhibitory concentration (MIC) was noted in µM and compared to ofloxacin and fluconazole...
August 12, 2018: Chemistry Central Journal
Yousry A Ammar, Ahmed M Sh El-Sharief, Amany Belal, Samir Y Abbas, Yehia A Mohamed, Ahmed B M Mehany, Ahmed Ragab
New series of 5-(morpholinosulfonyl) isatin derivatives were designed and synthesized. The new compounds were characterized on the basis of spectral and elemental analyses. They were examined for their cytotoxic effects using SRB assay on four cancer cell lines HepG2, HCT116, CACO and MCF-7 in addition to the non-cancerous human cell line. They were non cytotoxic towards the normal derived cell line (IC50 value > 130 μM). Compounds 3, 6, 10 and 11 showed IC50 values less than 10 μM on three of the tested cell lines HepG2, HCT116 and CACO...
June 28, 2018: European Journal of Medicinal Chemistry
Xiao-Yan Zhang, Zhan-Liang Liu, Bing-Da Da Sun, Shu-Bin Niu, Meng-Hua Wang, Xiang-Mei Tan, Zhong-Mei Zou, Gang Ding
Five new resorcylic acid lactones (RALs) hispidulactones A-E (1, 4, 5, 8, and 9), a new natural product (2) and four known ones (3, 6, 7 and 10) with different ring systems were isolated from the desert plant endophytic fungus Chaetosphaeronema hispidulur. The new compounds were characterized by NMR data, CD spectra, and X-ray experiment. The new natural product (2) displayed strongly biological effects on the seedlings growth of Arabidopsis thaliana, Digitaria sanguinalis and Echinochloa crusgalli with a dose-dependent relationship...
August 10, 2018: Journal of Agricultural and Food Chemistry
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