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PLC cancer calcium

Chi Huu Nguyen, Stefan Brenner, Nicole Huttary, Yuanfang Li, Atanas Georgiev Atanasov, Verena M Dirsch, Silvio Holzner, Serena Stadler, Juliane Riha, Sigurd Krieger, Danijela Milovanovic, Adryan Fristiohardy, Ingrid Simonitsch-Klupp, Helmut Dolznig, Philipp Saiko, Thomas Szekeres, Benedikt Giessrigl, Walter Jäger, Georg Krupitza
Secretion of 12(S)-HETE by breast cancer emboli provokes "circular chemorepellent induced defects" (CCIDs) in the adjacent lymphatic vasculature facilitating their intravasation and lymph node metastasis which determines prognosis. Therefore, elucidating the mechanism of lymph endothelial cell (LEC) wall disintegration may provide cues for anti-metastatic intervention. The role of intracellular free Ca(2+) for CCID formation was investigated in LECs using MCF-7 or MDA-MB231 breast cancer cell spheroids in a three-dimensional cell co-culture model...
September 28, 2016: Cancer Letters
Jóhannes Reynisson, Jagdish K Jaiswal, David Barker, Stacey A N D'mello, William A Denny, Bruce C Baguley, Euphemia Y Leung
BACKGROUND: The thieno[2,3-b]pyridines were discovered by virtual high throughput screening as potential inhibitors of phospholipase C (PLC) isoforms and showed potent growth inhibitory effects in National Cancer Institute's human tumour cell line panel (NCI60). The mechanism of the anti-proliferative activity of thieno[2,3-b]pyridines is explored here. OBJECTIVES: We aimed to investigate the basis for the anti-proliferative activity of these thieno[2,3-b]pyridines and to determine whether the cellular inhibition was related to their inhibition of PLC...
2016: Cancer Cell International
Wan-Jung Lu, Kao-Chang Lin, Chun-Ping Liu, Chia-Ying Lin, Hsh-Chu Wu, Duen-Suey Chou, Pitchairaj Geraldine, Shih-Yi Huang, Cheng-Ying Hsieh, Joen-Rong Sheu
Nobiletin, a bioactive polymethoxylated flavone isolated from citrus fruits, has been proven to prevent cancer and inflammation. Dietary flavonoids have been shown to reduce the risk of cardiovascular diseases (CVDs), and platelet activation plays a crucial role in CVDs. This study investigated the effect of nobiletin on platelet activation in vitro and in vivo. Nobiletin (10-30μM) inhibited collagen- and arachidonic acid-induced platelet aggregation in washed human platelets, but it did not inhibit platelet aggregation induced by other agonists such as thrombin and 9,11-dideoxy-11α,9α-epoxymethanoprostaglandin...
February 2016: Journal of Nutritional Biochemistry
Jae Youn Hwang, Chi Woo Yoon, Hae Gyun Lim, Jin Man Park, Sangpil Yoon, Jungwoo Lee, K Kirk Shung
Extracellular matrix proteins such as fibronectin (FNT) play crucial roles in cell proliferation, adhesion, and migration. For better understanding of these associated cellular activities, various microscopic manipulation tools have been used to study their intracellular signaling pathways. Recently, it has appeared that acoustic tweezers may possess similar capabilities in the study. Therefore, we here demonstrate that our newly developed acoustic tweezers with a high-frequency lithium niobate ultrasonic transducer have potentials to study intracellular calcium signaling by FNT-binding to human breast cancer cells (SKBR-3)...
December 2015: Ultrasonics
Chatchai Muanprasat, Preedajit Wongkrasant, Saravut Satitsri, Aekkacha Moonwiriyakit, Pawin Pongkorpsakol, Tharinee Mattaveewong, Rath Pichyangkura, Varanuj Chatsudthipong
Chitosan oligosaccharide (COS), a biomaterial derived from chitin, is absorbed by intestinal epithelia without degradation and has diverse biological activities including intestinal epithelial function. However, the mode of action is still unclear. This study aimed to investigate the effect of COS on AMP-activated protein kinase (AMPK) in intestinal epithelial cells (IEC) and its potential applications in the intestinal diseases benefited from AMPK activation. COS with molecular weights (MW) from 5,000Da to 14,000Da induced AMPK activation in T84 cells...
August 1, 2015: Biochemical Pharmacology
Neal D Andruska, Xiaobin Zheng, Xujuan Yang, Chengjian Mao, Mathew M Cherian, Lily Mahapatra, William G Helferich, David J Shapiro
Recurrent estrogen receptor α (ERα)-positive breast and ovarian cancers are often therapy resistant. Using screening and functional validation, we identified BHPI, a potent noncompetitive small molecule ERα biomodulator that selectively blocks proliferation of drug-resistant ERα-positive breast and ovarian cancer cells. In a mouse xenograft model of breast cancer, BHPI induced rapid and substantial tumor regression. Whereas BHPI potently inhibits nuclear estrogen-ERα-regulated gene expression, BHPI is effective because it elicits sustained ERα-dependent activation of the endoplasmic reticulum (EnR) stress sensor, the unfolded protein response (UPR), and persistent inhibition of protein synthesis...
April 14, 2015: Proceedings of the National Academy of Sciences of the United States of America
Maria Beatrice Morelli, Consuelo Amantini, Massimo Nabissi, Sonia Liberati, Claudio Cardinali, Valerio Farfariello, Daniele Tomassoni, Wilma Quaglia, Alessandro Piergentili, Alessandro Bonifazi, Fabio Del Bello, Matteo Santoni, Gabriele Mammana, Lucilla Servi, Alessandra Filosa, Angela Gismondi, Giorgio Santoni
BACKGROUND: There is evidence that calcium (Ca(2+)) increases the proliferation of human advanced prostate cancer (PCa) cells but the ion channels involved are not fully understood. Here, we investigated the correlation between alpha(1D)-adrenergic receptor (alpha(1D)-AR) and the transient receptor potential vanilloid type 1 (TRPV1) expression levels in human PCa tissues and evaluated the ability of alpha(1D)-AR to cross-talk with TRPV1 in PCa cell lines. METHODS: The expression of alpha1D-AR and TRPV1 was examined in human PCa tissues by quantitative RT-PCR and in PCa cell lines (DU145, PC3 and LNCaP) by cytofluorimetry...
2014: BMC Cancer
Jing-Yan Cheng, Sheng-Hung Wang, Juway Lin, Yi-Chien Tsai, John Yu, Jen-Chine Wu, Jung-Tung Hung, Jin-Jin Lin, Yih-Yiing Wu, Kun-Tu Yeh, Alice L Yu
Tumor angiogenesis is a critical element of cancer progression, and strategies for its selective blockade are still sought. Here, we examine the angiogenic effects of Globo-H ceramide (GHCer), the most prevalent glycolipid in a majority of epithelial cancers and one that acts as an immune checkpoint. Here, we report that GHCer becomes incorporated into endothelial cells through the absorption of microvesicles shed from tumor cells. In endothelial cells, GHCer addition induces migration, tube formation, and intracellular Ca(2+) mobilization in vitro and angiogenesis in vivo...
December 1, 2014: Cancer Research
N Andruska, X Zheng, X Yang, W G Helferich, D J Shapiro
In response to cell stress, cancer cells often activate the endoplasmic reticulum (EnR) stress sensor, the unfolded protein response (UPR). Little was known about the potential role in cancer of a different mode of UPR activation, anticipatory activation of the UPR prior to accumulation of unfolded protein or cell stress. We show that estrogen, acting via estrogen receptor α (ERα), induces rapid anticipatory activation of the UPR, resulting in increased production of the antiapoptotic chaperone BiP/GRP78, preparing cancer cells for the increased protein production required for subsequent estrogen-ERα-induced cell proliferation...
July 2015: Oncogene
Ko-Long Lin, Chiang-Ting Chou, Jin-Shiung Cheng, Hong-Tai Chang, Wei-Zhe Liang, Chun-Chi Kuo, I-Li Chen, Li-Ling Tseng, Pochuen Shieh, Ru-Fang Wu, Daih-Huang Kuo, Chung-Ren Jan
Fluoxetine is a serotonin-specific reuptake inhibitor that has been used as an antidepressant. This study examined the effect of fluoxetine on cytosolic free Ca²⁺ concentrations ([Ca2⁺]i) and viability in OC2 human oral cancer cells. The Ca²⁺-sensitive fluorescent dye fura-2 was used to measure [Ca²⁺]i, and the water soluble tetrazolium (WST-1) regent was used to measure viability. Fluoxetine induced [Ca²⁺]i rises concentration-dependently. The response was reduced by half by removing extracellular Ca²⁺...
October 31, 2014: Chinese Journal of Physiology
Wei-Zhe Liang, Chiang-Ting Chou, Hong-Tai Chang, Jin-Shiung Cheng, Daih-Huang Kuo, Kuang-Chung Ko, Ni-Na Chiang, Ru-Fang Wu, Pochuen Shieh, Chung-Ren Jan
Honokiol, an active constituent of oriental medicinal herb Magnolia officinalis, caused Ca(2+) mobilization and apoptosis in different cancer cells. In vivo, honokiol crossed the blood-brain or -cerebrospinal fluid barrier, suggesting that it may be an effective drug for the treatment of brain tumors, including glioblastoma. This study examined the effect of honokiol on intracellular Ca(2+) concentration ([Ca(2+)]i) and apoptosis in DBTRG-05MG human glioblastoma cells. Honokiol concentration-dependently induced a [Ca(2+)]i rise...
September 25, 2014: Chemico-biological Interactions
Shengqiang Zhao, Lei Zhou, Gengming Niu, Yan Li, Dezheng Zhao, Huiyan Zeng
Angiogenesis is a hallmark of many diseases, including cancer, ischemic heart disease, inflammation, and others. It is well known that vascular endothelial growth factor (VEGF) is the most important angiogenic factor. Recently, we demonstrated that orphan nuclear receptor TR3 (mouse Nur77 and rat NGFI-B) plays critical roles in tumor growth and angiogenesis induced by VEGF-A in vitro and in vivo. However, the signaling pathways that mediate the expression of TR3 induced by VEGF are still not completely understood...
October 2014: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
H-J Chang, C-T Chou, H-T Chang, W-Z Liang, T-Y Hung, Y-D Li, Y-C Fang, C-C Kuo, D-H Kuo, P Shieh, C-R Jan
Resveratrol is a natural compound that affects cellular calcium (Ca(2+)) homeostasis and viability in different cells. This study examined the effect of resveratrol on cytosolic free Ca(2+) concentrations ([Ca(2+)]i) and viability in OC2 human oral cancer cells. The Ca(2+)-sensitive fluorescent dye fura-2 was used to measure [Ca(2+)]i, and water-soluble tetrazolium-1 was used to measure viability. Resveratrol evoked concentration-dependent increase in [Ca(2+)]i. The response was reduced by removing extracellular Ca(2+)...
March 2015: Human & Experimental Toxicology
Jian Yang, Xiaomin Song, Yang Chen, Xin-an Lu, Yan Fu, Yongzhang Luo
The 90-kDa heat shock protein (Hsp90α) has been identified on the surface of cancer cells, and is implicated in tumor invasion and metastasis, suggesting that it is a potentially important target for tumor therapy. However, the regulatory mechanism of Hsp90α plasma membrane translocation during tumor invasion remains poorly understood. Here, we show that Hsp90α plasma membrane expression is selectively upregulated upon epidermal growth factor (EGF) stimulation, which is a process independent of the extracellular matrix...
August 2014: Traffic
Zahra Timsah, Zamal Ahmed, Chi-Chuan Lin, Fernando A Melo, Loren J Stagg, Paul G Leonard, Prince Jeyabal, Jonathan Berrout, Roger G O'Neil, Mikhail Bogdanov, John E Ladbury
FGFR2-expressing human cancer cells with low concentrations of the adaptor protein Grb2 show high prevalence for metastatic outcome. In nonstimulated cells, the SH3 domain (and not the SH2 domains) of Plcγ1 directly competes for a binding site at the very C terminus of FGFR2 with the C-terminal SH3 domain of Grb2. Reduction of Grb2 concentration permits Plcγ1 access to the receptor. Recruitment of Plcγ1 in this way is sufficient to upregulate phospholipase activity. This results in elevated phosphatidylinositol 4,5-bisphosphate turnover and intracellular calcium levels, thus leading to increased cell motility and promotion of cell-invasive behavior in the absence of extracellular receptor stimulation...
February 2014: Nature Structural & Molecular Biology
A-Young Choi, Ji Hyun Choi, Keun-Young Hwang, Yeon Ju Jeong, Wonchae Choe, Kyung-Sik Yoon, Joohun Ha, Sung Soo Kim, Jang Hyun Youn, Eui-Ju Yeo, Insug Kang
Licochalcone A (LicA), an estrogenic flavonoid, induces apoptosis in multiple types of cancer cells. In this study, the molecular mechanisms underlying the anti-cancer effects of LicA were investigated in HepG2 human hepatocellular carcinoma cells. LicA induced apoptotic cell death, activation of caspase-4, -9, and -3, and expression of endoplasmic reticulum (ER) stress-associated proteins, including C/EBP homologous protein (CHOP). Inhibition of ER stress by CHOP knockdown or treatment with the ER stress inhibitors, salubrinal and 4-phenylbutyric acid, reduced LicA-induced cell death...
April 2014: Apoptosis: An International Journal on Programmed Cell Death
Yuan-Li Huang, Chi-Lun Chang, Chih-Hsin Tang, Yueh-Chien Lin, Tsai-Kai Ju, Wei-Pang Huang, Hsinyu Lee
Sphingosine 1-phosphate (S1P) is a bioactive lysophospholipid that binds to a family of G protein-coupled receptors (GPCRs), termed S1P1-S1P5. Our previous study has reported that S1P induces autophagy in human prostate cancer PC-3 cell. In addition, S1P-induced autophagy plays a prosurvival role in PC-3 cells. Accumulating evidence has shown that the autophagy responses triggered by ER stress signaling have cytoprotective effects. Thus, we attempted to investigate whether S1P-induced autophagy is a result of triggering ER stress in PC-3 cells...
March 2014: Cellular Signalling
Luigi Catacuzzeno, Antonio Michelucci, Luigi Sforna, Francesco Aiello, Miriam Sciaccaluga, Bernard Fioretti, Emilia Castigli, Fabio Franciolini
The swelling-activated chloride current (I Cl,Vol) is abundantly expressed in glioblastoma (GBM) cells, where it controls cell volume and invasive migration. The transduction pathway mediating I Cl,Vol activation in GBM cells is, however, poorly understood. By means of pharmacological and electrophysiological approaches, on GL-15 human GBM cells we found that I Cl,Vol activation by hypotonic swelling required the activity of a U73122-sensitive phospholipase C (PLC). I Cl,Vol activation could also be induced by the membrane-permeable diacylglycerol (DAG) analog OAG...
January 2014: Journal of Membrane Biology
Shanshan Yin, Jianmin Zhang, Yujia Mao, Yu Hu, Lianxian Cui, Ning Kang, Wei He
T cell antigen receptor γδ (TCRγδ) and natural killer group 2, member D (NKG2D) are two crucial receptors for γδT cell cytotoxicity. Compelling evidences suggest that γδT cell cytotoxicity is TCRγδ-dependent and can be co-stimulated by NKG2D. However, the molecular mechanism of underlying TCRγδ-dependent activation of γδT cells remains unclear. In this study we demonstrated that TCRγδ but not NKG2D engagement induced lytic granule polarization and promoted γδT cell cytotoxicity. TCRγδ activation alone was sufficient to trigger Vav1-dependent phospholipase C-γ1 signaling, resulting in lytic granule polarization and effective killing, whereas NKG2D engagement alone failed to trigger cytotoxicity-related signaling to overcome the inhibitory effect of Cbl-b; therefore, NKG2D engagement alone could not induce effective killing...
September 13, 2013: Journal of Biological Chemistry
Chao-Chuan Chi, Chiang-Ting Chou, Wei-Zhe Liang, Chung-Ren Jan
Deltamethrin is a synthetic pyrethroid insecticide used extensively in pest control. Although deltamethrin has been shown to induce cytosolic free Ca(2+) concentration ([Ca(2+)]i) rises and apoptosis in different cancer cells, there is no information concerning the effects of deltamethrin on oral cancer. This study explored the effects of deltamethrin on [Ca(2+)]i and viability in OC2 human oral cancer cells. Deltamethrin, at concentrations of 5-10 μM, increased [Ca(2+)]i in a concentration-dependent manner...
January 2014: Drug and Chemical Toxicology
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