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PLC cancer calcium

Sayuri Suzuki, Annette Lis, Carsten Schmitz, Reinhold Penner, Andrea Fleig
The melastatin-related transient receptor potential member 7 (TRPM7) is a unique fusion protein with both ion channel function and enzymatic α-kinase activity. TRPM7 is essential for cellular systemic magnesium homeostasis and early embryogenesis; it promotes calcium transport during global brain ischemia and emerges as a key player in cancer growth. TRPM7 channels are negatively regulated through G-protein-coupled receptor-stimulation, either by reducing cellular cyclic adenosine monophosphate (cAMP) or depleting phosphatidylinositol bisphosphate (PIP2 ) levels in the plasma membrane...
March 2, 2018: Cellular and Molecular Life Sciences: CMLS
Hyun-Jun Jang, Pann-Ghill Suh, Yu Jin Lee, Kyeong Jin Shin, Lucio Cocco, Young Chan Chae
Phospholipase C (PLC) is an essential mediator of cellular signaling. PLC regulates multiple cellular processes by generating bioactive molecules such as inositol-1,4,5-triphosphate (IP3 ) and diacylglycerol (DAG). These products propagate and regulate cellular signaling via calcium (Ca2+ ) mobilization and activation of protein kinase C (PKC), other kinases, and ion channels. PLCγ1, one of the primary subtypes of PLC, is directly activated by membrane receptors, including receptor tyrosine kinases (RTKs), and adhesion receptors such as integrin...
January 2018: Advances in Biological Regulation
Amir Tajbakhsh, Alireza Pasdar, Mehdi Rezaee, Mostafa Fazeli, Saman Soleimanpour, Seyed Mahdi Hassanian, Zahra FarshchiyanYazdi, Tayebe Younesi Rad, Gordon A Ferns, Amir Avan
Calcium ions (Ca2+ ) act as second messengers in intracellular signaling. Ca2+ pumps, channels, sensors, and calcium binding proteins, regulate the concentrations of intracellular Ca2+ as a key regulator of important cellular processes such as gene expression, proliferation, differentiation, DNA repair, apoptosis, metastasis, and hormone secretion. Intracellular Ca2+ also influences the functions of several organelles, that include: the endoplasmic reticulum, mitochondria, the Golgi, and cell membrane both in normal and breast cancer cells...
August 2018: Journal of Cellular Physiology
Qian Sun, Jin Wang, Yao Li, Jingjing Zhuang, Qian Zhang, Xiao Sun, Dequn Sun
Artemisinin is a naturally occurring antimalarial agent which has shown potent anticancer activity. In this work, new artemisinin derivatives with the piperazine group were synthesized. The cytotoxic activities of derivatives 5a-5d were evaluated by MTT assay against ten cell lines. The results showed that 5a-5d were more effective in inhibiting cancer cell growth than artemisinin. 5d was the most active against HepG2 and PLC-PRF-5 cells and presented no cytotoxicity on L-02 cells. Hoechst 33342 staining and flow cytometry experiment revealed that 5d could induce HepG2 and PLC-PRF-5 cell apoptosis...
November 2017: Chemical Biology & Drug Design
Yuan-Lang Hu, Xue Mi, Chao Huang, Hui-Fang Wang, Jian-Ren Song, Qing Shu, Lan Ni, Jian-Guo Chen, Fang Wang, Zhuang-Li Hu
Acidosis has been known to cause "Ca(2+) transients", however, the mechanism is still uncertain. Here, we demonstrated that multiple H(+) sensors, such as ASICs, TRPV1 and proton-sensing G protein coupled receptors (GPCRs) are involved in extracellular acidification-induced intracellular calcium ([Ca(2+)]i) elevation. By using calcium imaging measures, we observed that both ASIC and TRPV1 channels inhibitors suppressed the [Ca(2+)]i elevation induced by extracellular acidosis in cultured rat cardiac myocytes...
March 23, 2017: Scientific Reports
Lea Weber, Klaudia Al-Refae, Juliane Ebbert, Peter Jägers, Janine Altmüller, Christian Becker, Stephan Hahn, Günter Gisselmann, Hanns Hatt
The analysis and functional characterization of ectopically expressed human olfactory receptors (ORs) is becoming increasingly important, as many ORs have been identified in several healthy and cancerous tissues. OR activation has been demonstrated to have influence on cancer cell growth and progression. Here, ORs were identified using RNA-Seq analyses and RT-PCR. We demonstrated the OR protein localization in HCT116 cells using immunocytochemistry (IHC). In order to analyze the physiological role of OR51B4, we deorphanized the receptor by the use of CRE-Luciferase assays, conducted calcium imaging experiments as well as scratch- and proliferation assays...
2017: PloS One
Serena Stadler, Chi Huu Nguyen, Helga Schachner, Daniela Milovanovic, Silvio Holzner, Stefan Brenner, Julia Eichsteininger, Mira Stadler, Daniel Senfter, Liselotte Krenn, Wolfgang M Schmidt, Nicole Huttary, Sigurd Krieger, Oskar Koperek, Zsuzsanna Bago-Horvath, Konstantin Alexander Brendel, Brigitte Marian, Oliver de Wever, Robert M Mader, Benedikt Giessrigl, Walter Jäger, Helmut Dolznig, Georg Krupitza
Retraction of mesenchymal stromal cells supports the invasion of colorectal cancer cells (CRC) into the adjacent compartment. CRC-secreted 12(S)-HETE enhances the retraction of cancer-associated fibroblasts (CAFs) and therefore, 12(S)-HETE may enforce invasivity of CRC. Understanding the mechanisms of metastatic CRC is crucial for successful intervention. Therefore, we studied pro-invasive contributions of stromal cells in physiologically relevant three-dimensional in vitro assays consisting of CRC spheroids, CAFs, extracellular matrix and endothelial cells, as well as in reductionist models...
May 2017: Cellular and Molecular Life Sciences: CMLS
Appalaraju Jaggupilli, Nisha Singh, Jasbir Upadhyaya, Anurag S Sikarwar, Makoto Arakawa, Shyamala Dakshinamurti, Rajinder P Bhullar, Kangmin Duan, Prashen Chelikani
The 25 bitter taste receptors (T2Rs) in humans perform a chemosensory function. However, very little is known about the level of expression of these receptors in different tissues. In this study, using nCounter gene expression we analyzed the expression patterns of human TAS2R transcripts in cystic fibrosis bronchial epithelial (CuFi-1), normal bronchial epithelial (NuLi-1), airway smooth muscle (ASM), pulmonary artery smooth muscle (PASM), mammary epithelial, and breast cancer cells. Our results suggest a specific pattern of TAS2R expression with TAS2R3, 4, 5, 10, 13, 19, and 50 transcripts expressed at moderate levels and TAS2R14 and TAS2R20 (or TASR49) at high levels in the various tissues analyzed...
February 2017: Molecular and Cellular Biochemistry
Jianhua Chen, Pei Gao, Sujing Yuan, Rongxin Li, Aimin Ni, Liang Chu, Li Ding, Ying Sun, Xin-Yuan Liu, Yourong Duan
Oncolytic adenovirus (Onco(Ad)) is a promising therapeutic agent for treating cancer. However, the therapeutic potential of Onco(Ad) is hindered by hepatic sequestration and the host immune response in vivo. Here, we constructed a PEG/Lipids/calcium phosphate (CaP)-Onco(Ad) (PLC-Onco(Ad)) delivery system for ZD55-IL-24, an oncolytic adenovirus that carries the IL-24 gene. The negatively charged PLC-ZD55-IL-24 were disperse and resisted serum-induced aggregation. Compared to naked ZD55-IL-24, the systemic administration of PLC-ZD55-IL-24 in BALB/c mice resulted in reduced liver sequestration and systemic toxicity and evaded the innate immune response...
December 27, 2016: ACS Nano
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
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