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https://www.readbyqxmd.com/read/28734953/estimating-relative-mitochondrial-dna-copy-number-using-high-throughput-sequencing-data
#1
Pan Zhang, Brian D Lehmann, David C Samuels, Shilin Zhao, Ying-Yong Zhao, Yu Shyr, Yan Guo
We hypothesize that the relative mitochondria copy number (MTCN) can be estimated by comparing the abundance of mitochondrial DNA to nuclear DNA reads using high throughput sequencing data. To test this hypothesis, we examined relative MTCN across 13 breast cancer cell lines using the RT-PCR based NovaQUANT Human Mitochondrial to Nuclear DNA Ratio Kit as the gold standard. Six distinct computational approaches were used to estimate the relative MTCN in order to compare to the RT-PCR measurements. The results demonstrate that relative MTCN correlates well with the RT-PCR measurements using exome sequencing data, but not RNA-seq data...
July 19, 2017: Genomics
https://www.readbyqxmd.com/read/28733324/nadph-oxidase-2-derived-superoxide-drives-mitochondrial-transfer-from-bone-marrow-stromal-cells-to-leukemic-blasts
#2
Christopher R Marlein, Lyubov Zaitseva, Rachel E Piddock, Stephen Robinson, Dylan Edwards, Manar S Shafat, Zhigang Zhou, Matthew Lawes, Kristian M Bowles, Stuart A Rushworth
Improvements in the understanding of the metabolic cross-talk between cancer and its micro-environment are expected to lead to novel therapeutic approaches. Acute myeloid leukemia (AML) cells have increased mitochondria compared to non-malignant CD34+ hematopoietic progenitor cells. Furthermore, contrary to the Warburg hypothesis, (AML) relies on oxidative phosphorylation to generate ATP. Here we report that in human AML, NOX2 generates superoxide which stimulates bone marrow stromal cells (BMSC) to AML blast transfer of mitochondria through AML derived tunnelling nanotubes...
July 21, 2017: Blood
https://www.readbyqxmd.com/read/28732061/melatonin-pre-treatment-mitigates-shsy-5y-cells-against-oxaliplatin-induced-mitochondrial-stress-and-apoptotic-cell-death
#3
Mohammad Waseem, Upasana Sahu, Mohd Salman, Arnab Choudhury, Sudeshna Kar, Heena Tabassum, Suhel Parvez
Oxaliplatin (Oxa) treatment to SH-SY5Y human neuroblastoma cells has been shown by previous studies to induce oxidative stress, which in turn modulates intracellular signaling cascades resulting in cell death. While this phenomenon of Oxa-induced neurotoxicity is known, the underlying mechanisms involved in this cell death cascade must be clarified. Moreover, there is still little known regarding the roles of neuronal mitochondria and cytosolic compartments in mediating Oxa-induced neurotoxicity. With a better grasp of the mechanisms driving neurotoxicity in Oxa-treated SH-SY5Y cells, we can then identify certain pathways to target in protecting against neurotoxic cell damage...
2017: PloS One
https://www.readbyqxmd.com/read/28730971/apoptosis-and-anti-cancer-drug-discovery-the-power-of-medicinal-fungi-and-plants
#4
Jack Ho Wong, Stephen Cho Wing Sze, Tzi Bun Ng, Randy Chi Fai Cheung, Chit Tam, Kalin Yanbo Zhang, Xiuli Dan, Yau Sang Chan, William Chi Shing Cho, Charlene Cheuk Wing Ng, Mary Miu Yee Waye, Weicheng Liang, Jinfang Zhang, Jie Yang, Xiuyun Ye, Juan Lin, Xiujuan Ye, Hexiang Wang, Fang Liu, David Wai Chan, Hextan Yuen Sheung Ngan, Ou Sha, Guohui Li, Ryan Tse, Tak Fu Tse, Helen Chan
The purpose of this account is to review the compounds capable of eliciting mitochondria-mediated apoptosis in cancer cells produced by medicinal fungi and plants. The medicinal fungi discussed encompass Cordyceps, Ganoderma species, Coriolus versicolor and Hypsizygus marmoreus. The medicinal plants discussed comprise Astragalus complanatus , Dendrobium spp,Dioscorea spp, Glycyrrhiza spp, Panax notoginseng, Panax ginseng, and Momordica charantia. These compounds have the potential of development into anticancer drugs...
July 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28730962/phosphonium-salt-displays-cytotoxic-effects-against-human-cancer-cell-lines
#5
Dhanyalayam Dhanya, Giuseppe Palma, AnnaRita Cappello, Annaluisa Mariconda, Maria Stefania Sinicropi, Francesca Giordano, Vitale Del Vecchio, Anna Ramunno, Claudio Arra, Pasquale Longo, Carmela Saturnino
Aims/ Objective: Phosphonium salts are compounds whose structural characteristics enable them to cross the plasma and mitochondrial membrane with ease. Cancer cells have higher plasma membrane potentials than normal cells, phosphonium salts selectively accumulate in the mitochondria of neoplastic cells and inhibit mitochondrial function. METHOD: In the presente work, we investigate the cytotoxic activity of lipophilic phosphonium salt (11-methoxy11-oxo-undecyl) triphenylphosphonium bromide (MUTP) as well as of two new phosphine oxide salts, 3,3'-(methylphosphoryl) dibenzenaminium chloride (SBAMPO) and 3,3' (phenylphosphoryl) dibenzenaminium chloride (SBAPPO) on the proliferation of breast cancer cell line (MCF-7) and human uterin cervix adenocarcinoma cells (HeLa)...
July 19, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28730486/phosphoproteomic-analysis-of-isolated-mitochondria-in-yeast
#6
Margaux Renvoisé, Ludovic Bonhomme, Marlène Davanture, Michel Zivy, Claire Lemaire
Mitochondria play a central role in cellular energy metabolism and cell death. Deregulation of mitochondrial functions is associated with several human pathologies (neurodegenerative diseases, neuromuscular diseases, type II diabetes, obesity, cancer). The steadily increasing number of identified mitochondrial phosphoproteins, kinases, and phosphatases in recent years suggests that reversible protein phosphorylation plays an important part in the control of mitochondrial processes. In addition, many mitochondrial phosphoproteins probably still remain to be identified, considering that 30% of proteins are expected to be phosphorylated in eukaryotes...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28729291/stimulator-of-ifn-genes-mediated-dna-sensing-pathway-is-suppressed-by-nlrp3-agonists-and-regulated-by-mitofusin-1-and-tbc1d15-mitochondria-dynamics-mediators
#7
Dohyeong Kwon, Eunbyeol Park, Suk-Jo Kang
The stimulator of IFN genes (STING)-mediated DNA-sensing pathway plays an important role in the innate immune response to pathogen infection, autoimmunity, and cancer; however, its regulatory mechanism has not been fully elucidated, and we do not yet know whether the STING pathway is counter-regulated by other innate immune pathways. Here, we show that the NLRP3-activating agonists, ATP and nigericin, prevent STING pathway activation in association with mitochondrial fragmentation; however, the suppression of the STING pathway and mitochondria fission were not dependent on NLRP3 or potassium efflux...
July 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28728544/cladosporol-a-triggers-apoptosis-sensitivity-by-ros-mediated-autophagic-flux-in-human-breast-cancer-cells
#8
Mytre Koul, Ashok Kumar, Ramesh Deshidi, Vishal Sharma, Rachna D Singh, Jasvinder Singh, Parduman Raj Sharma, Bhawal Ali Shah, Sundeep Jaglan, Shashank Singh
BACKGROUND: Endophytes have proven to be an invaluable resource of chemically diverse secondary metabolites that act as excellent lead compounds for anticancer drug discovery. Here we report the promising cytotoxic effects of Cladosporol A (HPLC purified >98%) isolated from endophytic fungus Cladosporium cladosporioides collected from Datura innoxia. Cladosporol A was subjected to in vitro cytotoxicity assay against NCI60 panel of human cancer cells using MTT assay. We further investigated the molecular mechanism(s) of Cladosporol A induced cell death in human breast (MCF-7) cancer cells...
July 20, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/28725634/ip3-receptor-mediated-calcium-signaling-and-its-role-in-autophagy-in-cancer
#9
REVIEW
Elzbieta Kania, Gemma Roest, Tim Vervliet, Jan B Parys, Geert Bultynck
Calcium ions (Ca(2+)) play a complex role in orchestrating diverse cellular processes, including cell death and survival. To trigger signaling cascades, intracellular Ca(2+) is shuffled between the cytoplasm and the major Ca(2+) stores, the endoplasmic reticulum (ER), the mitochondria, and the lysosomes. A key role in the control of Ca(2+) signals is attributed to the inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs), the main Ca(2+)-release channels in the ER. IP3Rs can transfer Ca(2+) to the mitochondria, thereby not only stimulating core metabolic pathways but also increasing apoptosis sensitivity and inhibiting basal autophagy...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28720775/metformin-ameliorates-the-phenotype-transition-of-peritoneal-mesothelial-cells-and-peritoneal-fibrosis-via-a-modulation-of-oxidative-stress
#10
Hyun-Soo Shin, Jiyeon Ko, Dal-Ah Kim, Eun-Sun Ryu, Hye-Myung Ryu, Sun-Hee Park, Yong-Lim Kim, Eok-Soo Oh, Duk-Hee Kang
Phenotype transition of peritoneum is an early mechanism of peritoneal fibrosis. Metformin, 5'-adenosine monophosphate-activated protein kinase (AMPK) activator, has recently received a new attention due to its preventive effect on organ fibrosis and cancer metastasis by inhibiting epithelial-to-mesenchymal transition (EMT). We investigated the effect of metformin on EMT of human peritoneal mesothelial cells (HPMC) and animal model of peritoneal dialysis (PD). TGF-β1-induced EMT in HPMC was ameliorated by metformin...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720668/efficient-mitochondrial-glutamine-targeting-prevails-over-glioblastoma-metabolic-plasticity
#11
Kristell Oizel, Cynthia Chauvin, Lisa Oliver, Catherine Gratas, Fanny Geraldo, Ulrich Jarry, Emmanuel Scotet, Marion Rabe, Marie-Clotilde Alves-Guerra, Raluca Teusan, Fabien Gautier, Delphine Loussouarn, Vincent Compan, Jean-Claude Martinou, François M Vallette, Claire Pecqueur
Purpose Glioblastoma (GBM) is the most common and malignant form of primary human brain tumor in adults, with an average survival at diagnosis of 18 months. Metabolism is a new attractive therapeutic target in cancer, however, little is known about metabolic heterogeneity and plasticity within GBM tumors. We therefore aimed to investigate metabolic phenotyping of primary cultures in the context of molecular tumor heterogeneity to provide a proof-of concept for personalized metabolic targeting of GBM. <p> Experimental Design We have analyzed extensively several primary GBM cultures using transcriptomics, metabolic phenotyping assays and mitochondrial respirometry...
July 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28720665/targeted-exome-sequencing-of-krebs-cycle-genes-reveals-candidate-cancer-predisposing-mutations-in-pheochromocytomas-and-paragangliomas
#12
Laura Remacha, Iñaki Comino-Méndez, Susan Richter, Laura Contreras, Maria Currás-Freixes, Guillermo Pita, Rocío Letón, Antonio Galarreta, Rafael Torres-Pérez, Emiliano Honrado, Scherezade Jiménez, Lorena Maestre, Sebastian Moran, Manel Esteller, Jorgina Satrústegui, Graeme Eisenhofer, Mercedes Robledo, Alberto Cascon
Purpose: Mutations in Krebs cycle genes are frequently found in patients with pheochromocytomas/paragangliomas. Disruption of SDH, FH or MDH2 enzymatic activities lead to accumulation of specific metabolites, which give rise to epigenetic changes in the genome that cause a characteristic hypermethylated phenotype. Tumors showing this phenotype, but no alterations in the known predisposing genes, could harbor mutations in other Krebs cycle genes. <p>Experimental Design: We used downregulation and methylation of RBP1, as a marker of a hypermethylation phenotype, to select eleven pheochromocytomas and paragangliomas for targeted exome sequencing of a panel of Krebs cycle-related genes...
July 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28718972/enhancement-of-mtor-signaling-contributes-to-acquired-x-ray-and-c-ion-resistance-in-mouse-squamous-carcinoma-cell-line
#13
Katsutoshi Sato, Rikako Azuma, Takashi Imai, Takashi Shimokawa
Our aim was to evaluate whether repetition of C-ion (carbon ion beam) irradiation induces radioresistance as well as repeated X-ray irradiation in cancer cell lines, and to find the key molecular pathway for radioresistance by comparing radioresistant cancer cells with their parental cells. A mouse squamous cell carcinoma cell line, NR-S1, and radioresistant cancer cells, NR-S1-C30 (C30) and NR-S1-X60 (X60) established by repetition of C-ion and X-ray irradiation respectively, were used. X-ray and C-ion sensitivity, changes in lysosome, mitochondria, intracellular ATP and ROS (reactive oxygen species) level, and mTOR (mechanistic target of rapamycin) signaling were evaluated...
July 18, 2017: Cancer Science
https://www.readbyqxmd.com/read/28718810/dna2-an-important-player-in-dna-damage-response-or-just-another-dna-maintenance-protein
#14
REVIEW
Elzbieta Pawłowska, Joanna Szczepanska, Janusz Blasiak
The human DNA2 (DNA replication helicase/nuclease 2) protein is expressed in both the nucleus and mitochondria, where it displays ATPase-dependent nuclease and helicase activities. DNA2 plays an important role in the removing of long flaps in DNA replication and long-patch base excision repair (LP-BER), interacting with the replication protein A (RPA) and the flap endonuclease 1 (FEN1). DNA2 can promote the restart of arrested replication fork along with Werner syndrome ATP-dependent helicase (WRN) and Bloom syndrome protein (BLM)...
July 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28716905/mitoneet-dependent-formation-of-intermitochondrial-junctions
#15
Alexandre Vernay, Anna Marchetti, Ayman Sabra, Tania N Jauslin, Manon Rosselin, Philipp E Scherer, Nicolas Demaurex, Lelio Orci, Pierre Cosson
MitoNEET (mNEET) is a dimeric mitochondrial outer membrane protein implicated in many facets of human pathophysiology, notably diabetes and cancer, but its molecular function remains poorly characterized. In this study, we generated and analyzed mNEET KO cells and found that in these cells the mitochondrial network was disturbed. Analysis of 3D-EM reconstructions and of thin sections revealed that genetic inactivation of mNEET did not affect the size of mitochondria but that the frequency of intermitochondrial junctions was reduced...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28716495/3-5-bis-3-dimethylaminomethyl-4-hydroxybenzylidene-4-piperidone-and-related-compounds-induce-glutathione-oxidation-and-mitochondria-mediated-cell-death-in-hct-116-colon-cancer-cells
#16
Eshwari Addala, Hossein Rafiei, Swagatika Das, Brian Bandy, Umashankar Das, Subhas S Karki, Jonathan R Dimmock
This study aims at investigating the cytotoxicity and some of the modes of action of 3,5-bis(3-dimethylamino-4-hydroxybenzylidene)-4-piperidone trihydrochloride 3 and two related compounds 2 (which lacks the dimethylaminomethyl groups) and 4 (which has an additional dimethylaminoethyl substituent in both aryl rings) in order to ascertain the contribution of dimethylaminoethyl substituent to bioactivity. The bioactivities of 2-4 were compared with curcumin 5. Both 2 and 3 displayed submicromolar GI50 values towards HCT-116 cells and were significantly more potent than 4, 5 and 5-fluorouracil (5-FU)...
July 5, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28714950/tid1-s-regulates-the-mitochondrial-localization-of-egfr-in-non-small-cell-lung-carcinoma
#17
T-H Wang, Y-H Lin, S-C Yang, P-C Chang, T-Cv Wang, C-Y Chen
The epidermal growth factor receptor (EGFR) is the major driver of non-small cell lung carcinoma (NSCLC). Mitochondrial accumulation of EGFR has been shown to promote metastasis in NSCLC, yet little is known about how the mitochondrial localization of EGFR is regulated. In this work, we show that Tid1 (also known as mitochondrial HSP40) is involved in the mitochondrial localization of EGFR, and that the DnaJ domain of Tid1-S is essential for the Tid1-S-mediated transportation of EGFR into mitochondria. Overexpression of Tid1-S increased the migration and invasion of NSCLC cells cultured in vitro...
July 17, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28714901/selenium-containing-polysaccharide-protein-complex-in-se-enriched-ulva-fasciata-induces-mitochondria-mediated-apoptosis-in-a549-human-lung-cancer-cells
#18
Xian Sun, Yu Zhong, Hongtian Luo, Yufeng Yang
The role of selenium (Se) and Ulva fasciata as potent cancer chemopreventive and chemotherapeutic agents has been supported by epidemiological, preclinical, and clinical studies. In this study, Se-containing polysaccharide-protein complex (Se-PPC), a novel organoselenium compound, a Se-containing polysaccharide-protein complex in Se-enriched Ulva fasciata, is a potent anti-proliferative agent against human lung cancer A549 cells. Se-PPC markedly inhibited the growth of cancer cells via induction of apoptosis which was accompanied by the formation of apoptotic bodies, an increase in the population of apoptotic sub-G1 phase cells, upregulation of p53, and activation of caspase-3 in A549 cells...
July 16, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28714351/activation-of-nlrp3-inflammasome-in-peripheral-nerve-contributes-to-paclitaxel-induced-neuropathic-pain
#19
Min Jia, Caihua Wu, Fang Gao, Hongchun Xiang, Ning Sun, Ping Peng, Jingjing Li, Xiaocui Yuan, Hongping Li, Xianfang Meng, Bo Tian, Jing Shi, Man Li
Background Paclitaxel is commonly used as a cancer chemotherapy drug that frequently causes peripheral neuropathic pain. Inflammasome is a multiprotein complex consisting of Nod-like receptor proteins (NLRPs), apoptosis-associated speck-like protein, and caspase-1, which functions to switch on the inflammatory process and the release of interleukin-1β. Growing evidences have supported that peripheral interleukin-1β is critical in enhancing paclitaxel-induced neuropathic pain. However, whether activation of NLRP3 inflammasome in peripheral nerve contributes to paclitaxel-induced neuropathic pain is still unclear...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28714224/codelivery-for-paclitaxel-and-bcl-2-conversion-gene-by-phb-pdmaema-amphiphilic-cationic-copolymer-for-effective-drug-resistant-cancer-therapy
#20
Xiaoyuan Wang, Sing Shy Liow, Qiaoqiong Wu, Chuang Li, Cally Owh, Zibiao Li, Xian Jun Loh, Yun-Long Wu
Antiapoptotic Bcl-2 protein's upregulated expression is a key reason for drug resistance leading to failure of chemotherapy. In this report, a series of biocompatible amphiphilic cationic poly[(R)-3-hydroxybutyrate] (PHB)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) copolymer, comprising hydrophobic PHB block and cationic PDMAEMA block, is designed to codeliver hydrophobic chemotherapeutic paclitaxel and Bcl-2 converting gene Nur77/ΔDBD with enhanced stability, due to the micelle formation by hydrophobic PHB segment...
July 17, 2017: Macromolecular Bioscience
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