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Wen-Peng Zhao, Hong-Wei Wang, Jing Liu, Pan-Pan Tan, Lin Lin, Bian-Hua Zhou
Excessive fluoride (F) intake decreases the development of potential oocytes by inducing oxidative stress and apoptosis in female mice in our previous study. This study aims to investigate the underlying mechanisms of F-induced follicular developmental dysplasia. Pathomorphological changes in the ovary tissues were observed under light and transmission electron microscopes. DNA damage and proliferation in granulosa cells were analysed by TUNEL staining and BrdU measurement. The protein expression of cell proliferation related regulatory factors including JNK, STAT3, STAT5, CDK2, CDK4, PCNA and Ki67 in the ovary tissues was measured by immunohistochemistry and Western blot analyses...
June 12, 2018: Chemosphere
Seung-Shick Shin, Dae-Hwa Noh, Byungdoo Hwang, Jo-Won Lee, Sung Lyea Park, Sung-Soo Park, Bokyung Moon, Wun-Jae Kim, Sung-Kwon Moon
Background: Although the diverse biological properties of nanoparticles have been studied intensively, research into their mechanism of action is relatively rare. In this study, we investigated the molecular mechanisms of the anticancer activity of heterometallic Au@Pt-nanoseeds (NSs) against bladder cancers. Materials and methods: Mode of action of Au@Pt-NSs was investigated through MTT assay, flow cytometry analysis, Western immunoblots, real-time qPCR, wound-healing migration and invasion assays, zymography, and electrophoretic mobility shift assay (EMSA)...
2018: International Journal of Nanomedicine
Leighton H Daigh, Chad Liu, Mingyu Chung, Karlene A Cimprich, Tobias Meyer
Faithful DNA replication is challenged by stalling of replication forks during S phase. Replication stress is further increased in cancer cells or in response to genotoxic insults. Using live single-cell image analysis, we found that CDK2 activity fluctuates throughout an unperturbed S phase. We show that CDK2 fluctuations result from transient ATR signals triggered by stochastic replication stress events. In turn, fluctuating endogenous CDK2 activity causes corresponding decreases and increases in DNA synthesis rates, linking changes in stochastic replication stress to fluctuating global DNA replication rates throughout S phase...
June 4, 2018: Cell Systems
Hung-Chuan Chiu, Wei-Ru Huang, Tsai-Ling Liao, Pei-I Chi, Brent L Nielsen, Jyung-Hurng Liu, Hung-Jen Liu
The avian reovirus (ARV) p17 protein is a nucleocytoplasmic shuttling protein. Although we have demonstrated that p17 causes cell growth retardation via activation of p53, the precise mechanisms remains unclear. This is the first report that ARV p17 possesses broad inhibitory effects on cell-cycle CDKs, cyclins, CDK/cyclin complexes, and CDK activating kinase (CAK) activity in various mammalian, avian, and cancer cell lines. Suppression of CDK activity by p17 occurs by direct binding to CDKs, cyclins, and CDK/cyclin complexes, transcriptional downregulation of CDKs, cytoplasmic retention of CDKs and cyclins, and inhibition of CAK activity by promoting p53/cyclin H interaction...
June 15, 2018: Journal of Biological Chemistry
Tianyi Wang, Minwen Ha
Breast cancer (BC) is one of the most common malignant tumors in women, and screening relevant genes and markers that are involved in BC tumor genesis and progression is of great value. We previously found that messenger RNA expression of ARHGAP9 was high in BC tissue, but it is unclear whether ARHGAP9 participates in the progression of human BC. In this study, we found that ARHGAP9 expression was correlated with poor patient survival, American Joint Committee on Cancer clinical staging, tumor size, and tumor differentiation...
June 15, 2018: Journal of Cellular Biochemistry
Gyeong-Ji Kim, Hyeon-Ju Jo, Kwon-Jai Lee, Jeong Woo Choi, Jeung Hee An
We evaluated oleanolic acid (OA)-induced anti-cancer activity, apoptotic mechanism, cell cycle status, and MAPK kinase signaling in DU145 (prostate cancer), MCF-7 (breast cancer), U87 (human glioblastoma), normal murine liver cell (BNL CL.2) and human foreskin fibroblast cell lines (Hs 68). The IC50 values for OA-induced cytotoxicity were 112.57 in DU145, 132.29 in MCF-7, and 163.60 in U87 cells, respectively. OA did not exhibit toxicity in BNL CL. 2 and Hs 68 cell lines in our experiments. OA, at 100 µg/mL, increased the number of apoptotic cells to 27...
May 29, 2018: Oncotarget
Yuki Kobayashi, Kan Tanaka
We previously showed that nuclear DNA replication (NDR) is regulated by a checkpoint monitoring the occurrence of organelle DNA replication (ODR) in a unicellular red alga Cyanidioschyzon merolae. These analyses depended on the use of chemical CDK inhibitors such as CDK2 inhibitor II and roscovitine, but subsequent analyses yielded conflicting results depending on the experimental conditions. In the present study, we identified significantly short half-lives of the used chemicals in the sulfur acidic cultivation medium, which reconciles the discrepancy among these results...
June 14, 2018: Journal of General and Applied Microbiology
Zhenyong Tang, Lei Li, Yuntian Tang, Dongyi Xie, Kun Wu, Weiyuan Wei, Qiang Xiao
Although significant progress has been made in the diagnosis and treatment of gastric cancer, the overall survival rate of the disease remains unchanged at approximately 20-25%. Thus, there is an urgent need for a better understanding of the molecular biology aspects of the disease, in the hope of discovering novel diagnosis and treatment strategies. Recent years have witnessed the decisive roles of aberrant cancer cell metabolism in the maintenance of malignant hallmarks of cancers, and cancer cell metabolism has been regarded as a novel target for the treatment of cancer...
June 13, 2018: Cancer Science
Xiaoru Xin, Mengying Wu, Qiuyu Meng, Chen Wang, Yanan Lu, Yuxin Yang, Xiaonan Li, Qidi Zheng, Hu Pu, Xin Gui, Tianming Li, Jiao Li, Song Jia, Dongdong Lu
BACKGROUND: Long noncoding RNA HULC is highly up-regulation in human hepatocellular carcinoma (HCC). However, the functions of HULC in hepatocarcinogenesis remains unclear. METHODS: RT-PCR, Western blotting, Chromatin immunoprecipitation (CHIP) assay, RNA Immunoprecipitation (RIP) and tumorignesis test in vitro and in vivo were performed. RESULTS: HULC is negatively associated with expression of PTEN or miR15a in patients of human liver cancer...
June 12, 2018: Molecular Cancer
Yonghao Tian, Hanxiang Chen, Lijun Qiao, Wenhao Zhang, Jingyi Zheng, Weiming Zhao, Jason J Chen, Weifang Zhang
Infection with high-risk human papillomaviruses (HR-HPVs, including HPV-16, HPV-18, HPV-31) plays a central aetiologic role in the development of cervical carcinoma. The transforming properties of HR-HPVs mainly reside in viral oncoproteins E6 and E7. E6 protein degrades the tumour suppressor p53 and abrogates cell cycle checkpoints. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein that is involved in the carcinogenesis of many human malignancies. Our previous data showed that CIP2A was overexpressed in cervical cancer...
June 12, 2018: Journal of Cellular and Molecular Medicine
Rita M Borik, Nagwa M Fawzy, Sherifa M Abu-Bakr, Magdy S Aly
Curcumin, a widely utilized flavor and coloring agent in food, has been shown to demonstrate powerful antioxidant, antitumor promoting and anti-inflammatory properties in vitro and in vivo. In the present work, synthesis of new heterocyclic derivatives based on Curcumin was studied. Compound 3 was synthesized via the reaction of furochromone carbaldehyde ( 1 ) with Curcumin ( 2 ) using pipredine as catalyst. Also, novel, 4,9-dimethoxy-5 H -furo [3, 2- g ] chromen-5-one derivatives 4a ⁻ d , 6a ⁻ d , 7 , 8a ⁻ d , 9 and 10 were synthesized by the reactions of furochromone carbaldehyde ( 1 ) with different reagents (namely: appropriate amine 3a ⁻ d , appropriate hydrazine 5a ⁻ d , hydroxylamine hydrochloride, urea/thiourea, malononitrile, malononitrile with hydrazine hydrate)...
June 8, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Dan Liu, Pengtao You, Yan Luo, Min Yang, Yanwen Liu
AIMS: The study aimed to investigate the molecular mechanism of inhibition of proliferation and apoptosis induction by galangin against MCF-7 human breast cancer cells. METHODS: Cell Counting Kit-8 assay was used to assess cell viability and flow cytometry was used to detect cell apoptosis. The expression level of apoptosis-related proteins (cleaved-caspase-9, cleaved-caspase-8, cleaved-caspase-3, Bad, cleaved-Bid, Bcl-2, Bax, p-phosphatidylinositol 3-kinase [PI3K], and p-Akt) and cell cycle-related proteins (cyclin D3, cyclin B1, cyclin-dependent kinases CDK1, CDK2, CDK4, p21, p27, p53) were evaluated by Western blotting...
June 7, 2018: Pharmacology
Jamila Soomro, Zhongyan Lu, Hongbing Gui, Bei Zhang, Zanming Shen
In our previous study, we demonstrated that butyrate induced ruminal epithelial growth through cyclin D1 upregulation. Here, we investigated the influence of butyrate on the expression of genes associated with cell cycle and apoptosis in rumen epithelium. Goats ( n = 24) were given an intra ruminal infusion of sodium butyrate at 0.3 (group B, n = 12) or 0 (group A, n = 12) g/kg of body weight (BW) per day before morning feeding for 28 days and were slaughtered (4 goat/group) at 5,7 and 9 h after butyrate infusion...
2018: Frontiers in Physiology
Steven D Cappell, Kevin G Mark, Damien Garbett, Lindsey R Pack, Michael Rape, Tobias Meyer
Mammalian cells integrate mitogen and stress signalling before the end of G1 phase to determine whether or not they enter the cell cycle1-4 . Before cells can replicate their DNA in S phase, they have to activate cyclin-dependent kinases (CDKs), induce an E2F transcription program and inactivate the anaphase-promoting complex (APC/CCDH1 , also known as the cyclosome), which is an E3 ubiquitin ligase that contains the co-activator CDH1 (also known as FZR, encoded by FZR1). It was recently shown that stress can return cells to quiescence after CDK2 activation and E2F induction but not after inactivation of APC/CCDH1 , which suggests that APC/CCDH1 inactivation is the point of no return for cell-cycle entry 3 ...
June 6, 2018: Nature
Zhuojia Lin, Yanan Lu, Qiuyu Meng, Chen Wang, Xiaonan Li, Yuxin Yang, Xiaoru Xin, Qidi Zheng, Jie Xu, Xin Gui, Tianming Li, Hu Pu, Wujun Xiong, Jiao Li, Song Jia, Dongdong Lu
MicroRNAs are known to be involved in carcinogenesis. Recently, microRNA-372 (miR372) has been proven to play a substantial role in several human cancers, but its functions in liver cancer remain unclear. Herein, our results demonstrate that miR372 accelerates growth of liver cancer cells in vitro and in vivo. Mechanistically, miR372 enhances expression of Y-box-binding protein 1 (YB-1) by targeting for phosphatase and tensin homolog (PTEN) directly and consequently promotes phosphorylation of YB-1 via HULC looping dependent on ERK1/2 and PTEN...
June 1, 2018: Molecular Therapy. Nucleic Acids
Agni F M Gavriilidou, Finn P Holding, Joseph E Coyle, Renato Zenobi
Native electrospray ionization mass spectrometry (ESI-MS) was applied to analyze the binding of compounds generated during fragment-based drug discovery (FBDD) campaigns against two functionally distinct proteins, the X-linked inhibitor of apoptosis protein (XIAP) and cyclin-dependent kinase 2 (CDK2). Compounds of different molecular weights and a wide range of binding affinities obtained from the hits to leads and lead optimization stages of FBDD campaigns were studied, and their dissociation constants (Kd ) were measured by native ESI-MS...
May 1, 2018: SLAS Discovery
Meng-Xian Lin, Sheng-Hao Lin, Chi-Chen Lin, Ching-Chieh Yang, Sheau-Yun Yuan
BACKGROUND/AIM: Pyrimethamine (PYR), an anti-malarial drug is known to inhibit various types of human cancer cells. The aim of this study was to investigate the anti-tumour effects of pyrimethamine (PYR) and its underlying molecular mechanisms using the human NSCLC cell line A549. MATERIALS AND METHODS: PYR was dissolved in dimethyl sulfoxide to determine its apoptotic activity on A549 cells. Cell viability was determined by the MTT assay. Cell cycle, mitochondrial membrane potential, and Annexin V-FITC early apoptosis detection were evaluated by flow cytometry...
June 2018: Anticancer Research
Kai Lin, Hong Jiang, Ling-Ling Zhang, Yi Jiang, Yu-Xian Yang, Guo-Dong Qiu, Yu-Qi She, Jie-Ting Zheng, Chen Chen, Ling Fang, Shu-Yao Zhang
BACKGROUND AND AIM: HOX transcript antisense intergenic RNA (HOTAIR) is a relatively well-understood RNA, which plays a central role in the pathogenesis of various tumors. The aim of the present study was to investigate the effect by which HOTAIR acts to influence the biological processes of colorectal cancer (CRC) through p21. METHODS: Reverse transcription quantitative polymerase chain reaction and Western blot methods were employed to provide verification regarding the changes in HOTAIR, PCNA, Ki67, p21, cyclin E, and CDK2 among the CRC tissues and cells...
May 28, 2018: Digestive Diseases and Sciences
Zhi-Lei Zhang, Guang-Chao Liu, Li Peng, Chong Zhang, Yu-Ming Jia, Wu-Han Yang, Lei Mao
This study intends to explore the effect of the PAK1 gene silencing on apoptosis and proliferation of hepatocellular carcinoma (HCC) MHCC97-H and HepG2 cells and cells in xenograft tumor. MHCC97-H and HepG2 cells and mice with xenograft tumor in vivo were randomly divided into control, empty vector and PAK1 shRNA groups. Morphology and the expression of green fluorescent protein of MHCC97-H and HepG2 cells and cells in xenograft tumor were observed. MTT assay and flow cytometry were used to detect proliferation, cell cycle and apoptosis of MHCC97-H and HepG2 cells and cells in xenograft tumor...
May 25, 2018: Gene Therapy
Pei Sun, Haoyang Wu, Jiali Huang, Ying Xu, Feng Yang, Qi Zhang, Xingang Xu
Porcine epidemic diarrhea virus (PEDV), an enteropathogenic Alphacoronavirus, has caused enormous economic losses in the swine industry. p53 protein exists in a wide variety of animal cells, which is involved in cell cycle regulation, apoptosis, cell differentiation and other biological functions. In this study, we investigated the effects of PEDV infection on the cell cycle of Vero cells and p53 activation. The results demonstrated that PEDV infection induces cell cycle arrest at G0/G1 phase in Vero cells, while UV-inactivated PEDV does not cause cell cycle arrest...
May 22, 2018: Virus Research
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