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https://www.readbyqxmd.com/read/28733545/a-small-molecule-inhibitor-targeting-the-aurkc-i%C3%AE%C2%BAb%C3%AE-interaction-decreases-transformed-growth-of-mda-mb-231-breast-cancer-cells
#1
Eun Hee Han, Jin-Young Min, Shin-Ae Yoo, Sung-Joon Park, Yun-Jeong Choe, Hee Sub Yun, Zee-Won Lee, Sun Woo Jin, Hyung Gyun Kim, Hye Gwang Jeong, Hyun Kyoung Kim, Nam Doo Kim, Young-Ho Chung
The Aurora kinases, Aurora A (AURKA), Aurora B (AURKB), and Aurora C (AURKC), are serine/threonine kinases required for the control of mitosis (AURKA and AURKB) or meiosis (AURKC). Several Aurora kinase inhibitors are being investigated as novel anticancer therapeutics. Recent studies demonstrated that AURKC activation contributes to breast cancer cell transformation. Therefore, AURKC is both a promising marker and therapeutic target for breast cancer; however, its signaling network has not been fully characterized...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28731136/mhy451-induces-cell-cycle-arrest-and-apoptosis-by-ros-generation-in-hct116-human-colorectal-cancer-cells
#2
Na Lam Hwang, Yong Jung Kang, Bokyung Sung, Seong Yeon Hwang, Jung Yoon Jang, Hye Jin Oh, Yu Ra Ahn, Do Hyun Kim, Su Jeong Kim, Sultan Ullah, Mohammad Akbar Hossain, Hyung Ryong Moon, Hae Young Chung, Nam Deuk Kim
Colorectal cancer (CRC) is the third most frequently diagnosed cancer and cause of cancer-related deaths. Despite advancements in conventional therapeutic approaches to CRC, most patients with CRC die of their disease. There is a need to develop novel therapeutic agents for this malignancy. Therefore, the present study aimed to examine the anticancer effects and elucidate the underlying mechanism of MHY451 in HCT116 human colorectal cancer cells. Treatment with MHY451 inhibited cell growth in a time- and concentration-dependent manner...
July 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28726723/mertensene-a-halogenated-monoterpene-induces-g2-m-cell-cycle-arrest-and-caspase-dependent-apoptosis-of-human-colon-adenocarcinoma-ht29-cell-line-through-the-modulation-of-erk-1-2-akt-and-nf-%C3%AE%C2%BAb-signaling
#3
Safa Tarhouni-Jabberi, Ons Zakraoui, Efstathia Ioannou, Ichrak Riahi-Chebbi, Meriam Haoues, Vassilios Roussis, Riadh Kharrat, Khadija Essafi-Benkhadir
Conventional treatment of advanced colorectal cancer is associated with tumor resistance and toxicity towards normal tissues. Therefore, development of effective anticancer therapeutic alternatives is still urgently required. Nowadays, marine secondary metabolites have been extensively investigated due to the fact that they frequently exhibit anti-tumor properties. However, little attention has been given to terpenoids isolated from seaweeds. In this study, we isolated the halogenated monoterpene mertensene from the red alga Pterocladiella capillacea (S...
July 20, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28692292/discovery-of-potent-and-selective-inhibitors-of-cdc2-like-kinase-1-clk1-as-a-new-class-of-autophagy-inducers
#4
Qi-Zheng Sun, Gui-Feng Lin, Lin-Li Li, Xi-Ting Jin, Lu-Yi Huang, Guo Zhang, Wei Yang, Kai Chen, Rong Xiang, Chong Chen, Yu-Quan Wei, Guang-Wen Lu, Sheng-Yong Yang
Autophagy inducers represent new promising agents for the treatment of a wide range of medical illnesses. However, safe autophagy inducers for clinical applications are lacking. Inhibition of cdc2-like kinase 1 (CLK1) was recently found to efficiently induce autophagy. Unfortunately, most of the known CLK1 inhibitors have unsatisfactory selectivity. Herein, we report the discovery of a series of new CLK1 inhibitors containing the 1H-[1,2,3]triazolo[4,5-c]quinoline scaffold. Among them, compound 25 was the most potent and selective, with an IC50 value of 2 nM against CLK1...
July 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28680385/angiopoietin-like-protein-4-potentiates-dats-induced-inhibition-of-proliferation-migration-and-invasion-of-bladder-cancer-ej-cells-involvement-of-g2-m-phase-cell-cycle-arrest-signaling-pathways-and-transcription-factors-mediated-mmp-9-expression
#5
Seung-Shick Shin, Jun-Hui Song, Byungdoo Hwang, Sung Lyea Park, Won Tae Kim, Sung-Soo Park, Wun-Jae Kim, Sung-Kwon Moon
Background: Diallyl trisulfide (DATS), a bioactive sulfur compound in garlic, has been highlighted due to its strong anti-carcinogenic activity. Objective: The current study investigated the molecular mechanism of garlic-derived DATS in cancer cells. Additionally, we explored possible molecular markers to monitoring clinical responses to DATS-based chemotherapy. Design: EJ bladder carcinoma cells were treated with different concentration of DATS. Molecular changes including differentially expressed genes in EJ cells were examined using immunoblot, FACS cell cycle analysis, migration and invasion assays, electrophoresis mobility shift assay (EMSA), microarray, and bioinformatics analysis...
2017: Food & Nutrition Research
https://www.readbyqxmd.com/read/28663269/inactivation-of-the-kinase-domain-of-cdk10-prevents-tumor-growth-in-a-preclinical-model-of-colorectal-cancer-and-is-accompanied-by-downregulation-of-bcl-2
#6
Louis-Bastien Weiswald, Mohammad R Hasan, John Ct Wong, Clarissa C Pasiliao, Mahbuba Rahman, Jianhua Ren, Yaling Yin, Samuel Gusscott, Sophie Vacher, Andrew P Weng, Hagen F Kennecke, Ivan Bièche, David F Schaeffer, Donald T Yapp, Isabella T Tai
Cyclin dependent kinase 10 (CDK10), a CDC2 related kinase, is highly expressed in colorectal cancer (CRC). Its role in the pathogenesis of CRC is unknown. This study examines the function of CDK10 in CRC, and demonstrates its role in suppressing apoptosis and in promoting tumor growth in vitro and in vivo Modulation of CDK10 expression in CRC cell lines demonstrates that CDK10 promotes cell growth, reduces chemosensitivity and inhibits apoptosis by upregulating the expression of Bcl-2. This effect appears to depend on its kinase activity, as kinase-defective mutant CRC cell lines have an exaggerated apoptotic response and reduced proliferative capacity...
June 29, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28661005/endogenous-bioelectric-currents-promote-differentiation-of-the-mammalian-lens
#7
Lin Cao, Jie Liu, Jin Pu, J Martin Collinson, John V Forrester, Colin D McCaig
The functional roles of bioelectrical signals (ES) created by the flow of specific ions at the mammalian lens equator are poorly understood. We detected that mature, denucleated lens fibers expressed high levels of the α1 and β1 subunits of Na(+) /K(+) -ATPase (ATP1A1 and ATP1B1 of the sodium pump) and had a hyperpolarized membrane potential difference (Vmem ). In contrast, differentiating, nucleated lens fibre cells had little ATP1A1 and ATP1B1 and a depolarized Vmem . Mimicking the natural equatorial ES with an applied electrical field (EF) induced a striking reorientation of lens epithelial cells to lie perpendicular to the direction of the EF...
June 29, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28621234/icarisid-ii-inhibits-the-proliferation-of-human-osteosarcoma-cells-by-inducing-apoptosis-and-cell-cycle-arrest
#8
Yuanyuan Tang, Mao Xie, Neng Jiang, Feifei Huang, Xiao Zhang, Ruishan Li, Jingjing Lu, Shijie Liao, Yun Liu
Icarisid II, one of the main active components of Herba Epimedii extracts, shows potent antitumor activity in various cancer cell lines, including osteosarcoma cells. However, the anticancer mechanism of icarisid II against osteosarcoma U2OS needs further exploration. This study aims to investigate further antitumor effects of icarisid II on human osteosarcoma cells and elucidate the underlying mechanism. We cultivated human osteosarcoma USO2 cells in vitro using different concentrations of icarisid II (0-30 µM)...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28591670/novel-synthetic-analogs-of-diallyl-disulfide-triggers-cell-cycle-arrest-and-apoptosis-via-ros-generation-in-mia-paca-2-cells
#9
Vikas Saini, Apra Manral, Rashi Arora, Poonam Meena, Siddharth Gusain, Daman Saluja, Manisha Tiwari
BACKGROUND: Diallyl disulfide (DADS), a principal organosulfur component of garlic, is known for its medicinal properties including anti-cancer activity. Prior studies have demonstrated that the compounds containing Diallyl disulfide moieties exhibited diverse therapeutic potential with promising biological activities. In the present study, we have investigated the in vitro anticancer activity of Diallyl disulfide derivatives (5a-5l and 7e-7m) against human cancer cell lines. METHODS: The effect of DADS analogs on different cancer cell lines was measured through MTT assay...
March 14, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28588709/growth-inhibition-of-human-breast-carcinoma-cells-by-overexpression-of-regulator-of-g-protein-signaling-4
#10
Hyun-Jung Park, Seung-Hyun Kim, Dong-Oh Moon
Breast cancer remains the second largest cause of mortality in women with cancer and does not respond well to conventional therapies. Regulator of G-protein signaling 4 (RGS4) is a GTPase-activating protein of the heterotrimeric Gq and Gi proteins. Altered levels of RGS4 are reportedly linked with several human diseases, including cancer. The present study investigated whether overexpression of RGS4 inhibited the growth of human breast cancer cells. Protein expression was investigated by western blot analysis...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28555643/development-of-an-orally-available-inhibitor-of-clk1-for-skipping-a-mutated-dystrophin-exon-in-duchenne-muscular-dystrophy
#11
Yukiya Sako, Kensuke Ninomiya, Yukiko Okuno, Masayasu Toyomoto, Atsushi Nishida, Yuka Koike, Kenji Ohe, Isao Kii, Suguru Yoshida, Naohiro Hashimoto, Takamitsu Hosoya, Masafumi Matsuo, Masatoshi Hagiwara
Duchenne muscular dystrophy (DMD) is a fatal progressive muscle-wasting disease. Various attempts are underway to convert severe DMD to a milder phenotype by modulating the splicing of the dystrophin gene and restoring its expression. In our previous study, we reported TG003, an inhibitor of CDC2-like kinase 1 (CLK1), as a splice-modifying compound for exon-skipping therapy; however, its metabolically unstable feature hinders clinical application. Here, we show an orally available inhibitor of CLK1, named TG693, which promoted the skipping of the endogenous mutated exon 31 in DMD patient-derived cells and increased the production of the functional exon 31-skipped dystrophin protein...
May 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28552434/protein-kinases-that-phosphorylate-splicing-factors-roles-in-cancer-development-progression-and-possible-therapeutic-options
#12
Alicja Czubaty, Agnieszka Piekiełko-Witkowska
Disturbed alternative splicing is a common feature of human tumors. Splicing factors that control alternative splicing are phosphorylated by multiple kinases, including these that specifically add phosphoryl groups to serine-arginine rich proteins (e.g. SR-protein kinases, cdc2-like kinases, topoisomerase 1), and protein kinases that govern key cellular signaling pathways (i.e. AKT). Phosphorylation of splicing factors regulates their subcellular localization and interactions with target transcripts and protein partners, and thus significantly contributes the final result of splicing reactions...
May 25, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28549347/the-roles-of-ing5-in-gliomas-a-good-marker-for-tumorigenesis-and-a-potential-target-for-gene-therapy
#13
Shuang Zhao, Zhi-Juan Zhao, Hao-Yu He, Ji-Cheng Wu, Xiao-Qing Ding, Lei Yang, Ning Jia, Zhi-Jie Li, Hua-Chuan Zheng
To elucidate the anti-tumor effects and molecular mechanisms of ING5 on glioma cells, we overexpressed it in U87 cells, and examined the phenotypes and their relevant molecules. It was found that ING5 overexpression suppressed proliferation, energy metabolism, migration, invasion, and induced G2/M arrest, apoptosis, dedifferentiation, senescence, mesenchymal- epithelial transition and chemoresistance to cisplatin, MG132, paclitaxel and SAHA in U87 cells. There appeared a lower expression of N-cadherin, Twist, Slug, Zeb1, Zeb2, Snail, Ac-H3, Ac-H4, Cdc2, Cdk4 and XIAP, but a higher expression of Claudin 1, Histones 3 and 4, p21, p53, Bax, β-catenin, PI3K, Akt, and p-Akt in ING5 transfectants...
May 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548966/targeting-shp-1-stat3-signaling-a-promising-therapeutic-approach-for-the-treatment-of-cholangiocarcinoma
#14
Ming-Hung Hu, Li-Ju Chen, Yen-Lin Chen, Ming-Shen Tsai, Chung-Wai Shiau, Tzu-I Chao, Chun-Yu Liu, Jia-Horng Kao, Kuen-Feng Chen
Sorafenib is a multiple kinase inhibitor which targets Raf kinases, VEGFR, and PDGFR and is approved for the treatment of hepatocellular carcinoma (HCC). Previously, we found that p-STAT3 is a major target of SC-43, a sorafenib derivative. In this study, we report that SC-43-induced apoptosis in cholangiocarcinoma (CCA) via a novel mechanism. Three CCA cell lines (HuCCT-1, KKU-100 and CGCCA) were treated with SC-43 to determine their sensitivity to SC-43-induced cell death and apoptosis. We found that SC-43 activated SH2 domain-containing phosphatase 1 (SHP-1) activity, leading to p-STAT3 and downstream cyclin B1 and Cdc2 downregulation, which induced G2-M arrest and apoptotic cell death...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548367/sinularin-induces-oxidative-stress-mediated-g2-m-arrest-and-apoptosis-in-oral-cancer-cells
#15
Yung-Ting Chang, Chang-Yi Wu, Jen-Yang Tang, Chiung-Yao Huang, Chih-Chuang Liaw, Shih-Hsiung Wu, Jyh-Horng Sheu, Hsueh-Wei Chang
Soft corals-derived natural product, sinularin, was antiproliferative against some cancers but its effect and detailed mechanism on oral cancer cells remain unclear. The subject of this study is to examine the antioral cancer effects and underlying detailed mechanisms in terms of cell viability, oxidative stress, cell cycle analysis, and apoptosis analyses. In MTS assay, sinularin dose-responsively decreased cell viability of three oral cancer cells (Ca9-22, HSC-3, and CAL 27) but only little damage to oral normal cells (HGF-1)...
May 26, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28539822/induction-of-mitotic-delay-in-pharyngeal-and-nasopharyngeal-carcinoma-cells-using-an-aqueous-extract-of-ajuga-bracteosa
#16
Yu-Tsai Lin, Chih-Che Lin, Hung-Chen Wang, Yi-Chiang Hsu
Nasopharyngeal carcinoma (NPC) is a common cancer in Southeast Asia, for which radiotherapy and/or chemotherapy are the primary treatment methods. Many herbs are known to have potential uses in chemotherapy; however, the mechanisms underlying the observed antitumor activity of Ajuga bracteosa (AB) against NPC remain unclear. We explored the antitumor effects of AB, which was shown specifically to induce mitotic delay in pharyngeal (Detroit 562) and nasopharyngeal (Hone-1) cancer cells. Proliferation of cancer cells after exposure to aqueous extract of A...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28534969/the-cdc2-cdk1-inhibitor-purvalanol-a-enhances-the-cytotoxic-effects-of-taxol-through-op18-stathmin-in-non-small-cell-lung-cancer-cells-in%C3%A2-vitro
#17
Xian Chen, Ying Liao, Dan Long, Ting Yu, Fang Shen, Xuechi Lin
Purvalanol A is a highly selective inhibitor of Cdc2 [also known as cyclin-dependent kinase 1 (CDK1)]. Taxol is an anti-tumor chemotherapeutic drug which is widely used clinically. In this study, the CDK1 inhibitor, purvalanol A was applied to explore the relevance of Cdc2 signaling and taxol sensitivity through analyses, such as cellular proliferation and apoptosis assays, ELISA, western blot analysis and immunoprecipitation. We demonstrated that purvalanol A effectively enhanced the taxol-induced apoptosis of NCI-H1299 cells, as well as its inhibitory effects on cellular proliferation and colony formation...
May 15, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28512026/one-pot-synthesis-and-biological-evaluation-of-n-aminosulfonyl-4-podophyllotoxin-carbamates-as-potential-anticancer-agents
#18
Xiao-Hui Xu, Xiao-Wen Guan, Shi-Liang Feng, You-Zhen Ma, Shi-Wu Chen, Ling Hui
A series of N-(aminosulfonyl)-4-podophyllotoxin carbamates were synthesized via the Burgess-type intermediate, and their antiproliferative activities were evaluated. Most of them possessed more potent cytotoxic effects against four human tumor cell lines (HeLa, A-549, HCT-8 and HepG2) and less toxic to normal human fetal lung fibroblast WI-38 cells than etoposide. In particular, N-(morpholinosulfonyl)-4-podophyllotoxin carbamate (9) exhibited the most potent activity towards these four tumor cells with IC50 values in the range of 0...
April 27, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28484902/the-molecular-mechanisms-of-protective-role-of-se-on-the-g2-m-phase-arrest-of-jejunum-caused-by-afb1
#19
Jing Fang, Heng Yin, Zhixiang Zheng, Panpan Zhu, Xi Peng, Zhicai Zuo, Hengmin Cui, Yi Zhou, Ping Ouyang, Yi Geng, Junliang Deng
Aflatoxin B1 (AFB1) is the most toxic among the mycotoxins and causes detrimental health effects on human and animals. Selenium (Se) plays an important role in chemopreventive, antioxidant, anticarcinogen, and detoxification and involved in cell cycle regulation. The aim of this study was to explore the molecular mechanisms of selenium involved in inhibition of G2/M cell cycle arrest of broiler's jejunum. A total of 240 one-day-old healthy Cobb broilers were randomly divided into four groups and fed with basal diet (control group), 0...
May 9, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28475750/astaxanthin-increases-radiosensitivity-in-esophageal-squamous-cell-carcinoma-through-inducing-apoptosis-and-g2-m-arrest
#20
X Qian, C Tan, B Yang, F Wang, Y Ge, Z Guan, J Cai
Nowadays esophageal squamous cell carcinoma (ESCC) is primarily treated by a comprehensive approach combining surgical resection and neoadjuvant chemo- or radiotherapy. However, ESCC is resistant to radiation therapy, resulting in its invasion, infiltration, and metastasis. It usually has rapidly progressed and has a poor outcome clinically. The purpose of this study is to determine the potential radiosensitizing effect of astaxanthin (ATX) and explore the underlying mechanisms in ESCC cells in vitro. ESCC cell lines were exposure to irradiation, in the presence or absence of ATX treatment...
June 1, 2017: Diseases of the Esophagus: Official Journal of the International Society for Diseases of the Esophagus
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