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Cancer mitochondria

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https://www.readbyqxmd.com/read/28938577/mitochondria-chaperone-grp75-moonlighting-as-a-cell-cycle-controller-to-derail-endocytosis-provides-an-opportunity-for-nanomicrosphere-intracellular-delivery
#1
Zhihui Gao, Xiuran Niu, Qing Zhang, Hang Chen, Aiai Gao, Shanshan Qi, Rong Xiang, Mattias Belting, Sihe Zhang
Understanding how cancer cells regulate endocytosis during the cell cycle could lead us to capitalize this event pharmacologically. Although certain endocytosis pathways are attenuated during mitosis, the endocytosis shift and regulation during the cell cycle have not been well clarified. The conventional concept of glucose-regulated proteins (GRPs) as protein folding chaperones was updated by discoveries that translocated GRPs assume moonlighting functions that modify the immune response, regulate viral release, and control intracellular trafficking...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28932704/cancer-linking-powerhouses-to-suicidal-bags
#2
REVIEW
Laia Martinez-Carreres, Anita Nasrallah, Lluis Fajas
Membrane-bound organelles are integrated into cellular networks and work together for a common goal: regulating cell metabolism, cell signaling pathways, cell fate, cellular maintenance, and pathogen defense. Many of these interactions are well established, but little is known about the interplay between mitochondria and lysosomes, and their deregulation in cancer. The present review focuses on the common signaling pathways of both organelles, as well as the processes in which they both physically interact, their changes under pathological conditions, and the impact on targeting those organelles for treating cancer...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28932118/fabrication-optimization-and-characterization-of-umbelliferone-%C3%AE-d-galactopyranoside-loaded-plga-nanoparticles-in-treatment-of-hepatocellular-carcinoma-in-vitro-and-in-vivo-studies
#3
Vikas Kumar, Prakash Chandra Bhatt, Mahfoozur Rahman, Gaurav Kaithwas, Hani Choudhry, Fahad A Al-Abbasi, Firoz Anwar, Amita Verma
Umbelliferone β-D-galactopyranoside (UFG), isolated from plants, exhibits promising inhibitory action on numerous diseases. The present research was initiated to develop a suitable delivery system for UFG with an intention to enhance its therapeutic efficacy against diethyl nitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in Wistar rats. UFG-loaded polymeric nanoparticles prepared by sonication were scrutinized for average size, drug loading capacity, zeta potential, and drug release potency in animals...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28931882/honokiol-protects-against-doxorubicin-cardiotoxicity-via-improving-mitochondrial-function-in-mouse-hearts
#4
Lizhen Huang, Kailiang Zhang, Yingying Guo, Fengyuan Huang, Kevin Yang, Long Chen, Kai Huang, Fengxue Zhang, Qinqiang Long, Qinglin Yang
Honokiol is a key component of a medicinal herb, Magnolia bark. Honokiol possesses potential pharmacological benefits for many disease conditions, especially cancer. Recent studies demonstrate that Honokiol exerts beneficial effects on cardiac hypertrophy and doxorubicin (Dox)-cardiotoxicity via deacetylation of mitochondrial proteins. However, the effects and mechanisms of Honokiol on cardiac mitochondrial respiration remain unclear. In the present study, we investigate the effect of Honokiol on cardiac mitochondrial respiration in mice subjected to Dox treatment...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28930681/parkin-independent-mitophagy-controls-chemotherapeutic-response-in-cancer-cells
#5
Elodie Villa, Emma Proïcs, Camila Rubio-Patiño, Sandrine Obba, Barbara Zunino, Jozef P Bossowski, Romain M Rozier, Johanna Chiche, Laura Mondragón, Joel S Riley, Sandrine Marchetti, Els Verhoeyen, Stephen W G Tait, Jean-Ehrland Ricci
Mitophagy is an evolutionarily conserved process that selectively targets impaired mitochondria for degradation. Defects in mitophagy are often associated with diverse pathologies, including cancer. Because the main known regulators of mitophagy are frequently inactivated in cancer cells, the mechanisms that regulate mitophagy in cancer cells are not fully understood. Here, we identified an E3 ubiquitin ligase (ARIH1/HHARI) that triggers mitophagy in cancer cells in a PINK1-dependent manner. We found that ARIH1/HHARI polyubiquitinates damaged mitochondria, leading to their removal via autophagy...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28930188/cytotoxic-and-apoptotic-activities-of-prunus-spinosa-trigno-ecotype-extract-on-human-cancer-cells
#6
Stefania Meschini, Evelin Pellegrini, Maria Condello, Giovanni Occhionero, Sebastiano Delfine, Giancarlo Condello, Franco Mastrodonato
The aim of this work was to demonstrate that a natural compound, not-toxic to normal cells, has cytotoxic and sensitizing effects on carcinoma cells, with the final goal of combining it with chemotherapeutic drugs to reduce the overall dose. Prunus spinosa Trigno ecotype (PsT) drupe extract with a nutraceutical activator complex (NAC) made of amino acids, vitamins and mineral salt blends, has shown in vitro anticancer activity. The cytotoxic effect of (PsT + NAC)(®) has been evaluated on human cancer cells, with an initial screening with colorectal, uterine cervical, and bronchoalveolar cells, and a subsequent focus on colon carcinoma cells HCT116 and SW480...
September 20, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28928246/exploiting-mitochondrial-and-oxidative-vulnerabilities-with-a-synthetic-analog-of-pancratistatin-in-combination-with-piperlongumine-for-cancer-therapy
#7
Dennis Ma, Tyler Gilbert, Christopher Pignanelli, Daniel Tarade, Megan Noel, Fadi Mansour, Manika Gupta, Sabrina Ma, Jesse Ropat, Colin Curran, Sergey Vshyvenko, Tomas Hudlicky, Siyaram Pandey
Harsh adverse effects as a result of nonspecific targeting of chemotherapeutics currently pose obstacles in cancer therapy; thus, it would be invaluable to devise novel approaches to specifically target cancer cells. The natural compound pancratistatin (PST) has been shown to preferentially induce apoptosis in a variety of cancer cell types. Recently, several analogs of PST were shown to be efficacious in inducing apoptosis in a variety of aggressive cancer cell types via cancer cell mitochondrial targeting; it caused dissipation of mitochondrial membrane potential and decreased oxygen consumption, and with isolated mitochondria, it induced the release of apoptogenic factors...
September 19, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28926928/curcumin-inhibited-growth-of-human-melanoma-a375-cells-via-inciting-oxidative-stress
#8
Wang Liao, Wei Xiang, Fei-Fei Wang, Rui Wang, Yan Ding
Curcumin, a polyphenol compound, possesses potent pharmacological properties in preventing cancers, which make it as a potential anti-cancer mediator. However, it is still unknown that whether Curcumin induced melanoma A375 cell was associated with oxidative stress. Here, we firstly found a fascinating result that Curcumin could reduce the proliferation and induced apoptosis of human melanoma A375 cells. Meanwhile, IC50 of Curcumin on A375 cells is 80μM at 48h. In addition, Curcumin caused oxidative stress through inducing further ROS burst, decreasing GSH, and wrecking mitochondria membrane potential (MMP), which were reversed by ROS inhibitor N-acetylcysteine (NAC)...
September 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28924745/hypertonia-linked-protein-trak1-functions-with-mitofusins-to-promote-mitochondrial-tethering-and-fusion
#9
Crystal A Lee, Lih-Shen Chin, Lian Li
Hypertonia is a neurological dysfunction associated with a number of central nervous system disorders, including cerebral palsy, Parkinson's disease, dystonia, and epilepsy. Genetic studies have identified a homozygous truncation mutation in Trak1 that causes hypertonia in mice. Moreover, elevated Trak1 protein expression is associated with several types of cancers and variants in Trak1 are linked to childhood absence epilepsy in humans. Despite the importance of Trak1 in health and disease, the mechanisms of Trak1 action remain unclear and the pathogenic effects of Trak1 mutation are unknown...
September 18, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28923495/crispr-cas9-engineering-of-adult-mouse-liver-demonstrates-that-the-dnajb1-prkaca-gene-fusion-is-sufficient-to-induce-tumors-resembling-fibrolamellar-hepatocellular-carcinoma
#10
Lars H Engelholm, Anjum Riaz, Denise Serra, Frederik Dagnæs-Hansen, Jens V Johansen, Eric Santoni-Rugiu, Steen H Hansen, Francesco Niola, Morten Frödin
BACKGROUND & AIMS: Fibrolamellar hepatocellular carcinoma (FL-HCC) is a primary liver cancer that predominantly affects young adults with no underlying liver disease. A somatic, 400 Kb deletion on chromosome 19 that fuses part of the DnaJ heat shock protein family (Hsp40) member B1 gene (DNAJB1) to the protein kinase cAMP-activated catalytic subunit alpha gene (PRKACA) has been repeatedly identified in patients with FL-HCC. However, the DNAJB1-PRKACA gene fusion has not been shown to induce liver tumorigenesis...
September 15, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28921987/a-novel-aryl-urea-fatty-acid-that-targets-the-mitochondrion-and-depletes-cardiolipin-to-promote-killing-of-breast-cancer-cells
#11
Tristan Rawling, Hassan Choucair, Nooshin Koolaji, Kirsi Bourget, Sarah E Allison, Yong-Juan Chen, Colin R Dunstan, Michael Murray
Cancer cell mitochondria are promising anticancer drug targets because they control cell death and are structurally and functionally different from normal cell mitochondria. We synthesized aryl-urea fatty acids and found that the analogue 16({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)hexadecanoic acid (13b) decreased proliferation and activated apoptosis in MDA-MB-231 breast cancer cells in vitro and in vivo. In mechanistic studies 13b emerged as the prototype of a novel class of mitochondrion-targeted agents that deplete cardiolipin and promote cancer cell death...
September 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28919040/heme-binding-biguanides-target-cytochrome-p450-dependent-cancer-cell-mitochondria
#12
Zhijun Guo, Irina F Sevrioukova, Ilia G Denisov, Xia Zhang, Ting-Lan Chiu, Dafydd G Thomas, Eric A Hanse, Rebecca A D Cuellar, Yelena V Grinkova, Vanessa Wankhede Langenfeld, Daniel S Swedien, Justin D Stamschror, Juan Alvarez, Fernando Luna, Adela Galván, Young Kyung Bae, Julia D Wulfkuhle, Rosa I Gallagher, Emanuel F Petricoin, Beverly Norris, Craig M Flory, Robert J Schumacher, M Gerard O'Sullivan, Qing Cao, Haitao Chu, John D Lipscomb, William M Atkins, Kalpna Gupta, Ameeta Kelekar, Ian A Blair, Jorge H Capdevila, John R Falck, Stephen G Sligar, Thomas L Poulos, Gunda I Georg, Elizabeth Ambrose, David A Potter
The mechanisms by which cancer cell-intrinsic CYP monooxygenases promote tumor progression are largely unknown. CYP3A4 was unexpectedly associated with breast cancer mitochondria and synthesized arachidonic acid (AA)-derived epoxyeicosatrienoic acids (EETs), which promoted the electron transport chain/respiration and inhibited AMPKα. CYP3A4 knockdown activated AMPKα, promoted autophagy, and prevented mammary tumor formation. The diabetes drug metformin inhibited CYP3A4-mediated EET biosynthesis and depleted cancer cell-intrinsic EETs...
August 29, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28917640/biotinylated-platinum-iv-complexes-designed-to-target-cancer-cells
#13
Jian Zhao, Wuyang Hua, Gang Xu, Shaohua Gou
Three biotinylated platinum(IV) complexes (1-3) were designed and synthesized. The resulting platinum(IV) complexes exhibited effective cytotoxicity against the tested cancer cell lines, especially complex 1, which was 2.0-9.6-fold more potent than cisplatin. These complexes were found to be rapidly reduced to their activated platinum(II) counterparts by glutathione or ascorbic acid under biologically relevant condition. Additional molecular docking studies revealed that the biotin moieties of all Pt(IV) complexes can effectively bind with the streptavidin through the noncovalent interactions...
August 26, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28915708/targeting-metabolism-and-amp-activated-kinase-with-metformin-to-sensitize-non-small-cell-lung-cancer-nsclc-to-cytotoxic-therapy-translational-biology-and-rationale-for-current-clinical-trials
#14
REVIEW
Michael Troncone, Stephanie M Cargnelli, Linda A Villani, Naghmeh Isfahanian, Lindsay A Broadfield, Laura Zychla, Jim Wright, Gregory Pond, Gregory R Steinberg, Theodoros Tsakiridis
Lung cancer is the most fatal malignancy worldwide, in part, due to high resistance to cytotoxic therapy. There is need for effective chemo-radio-sensitizers in lung cancer. In recent years, we began to understand the modulation of metabolism in cancer and its importance in tumor progression and survival after cytotoxic therapy. The activity of biosynthetic pathways, driven by the Growth Factor Receptor/Ras/PI3k/Akt/mTOR pathway, is balanced by the energy stress sensor pathway of LKB1/AMPK/p53. AMPK responds both to metabolic and genotoxic stress...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915639/heptamethine-carbocyanine-dz-1-dye-for-near-infrared-fluorescence-imaging-of-hepatocellular-carcinoma
#15
Jiaze An, Ningning Zhao, Caiqin Zhang, Yong Zhao, Dengxu Tan, Ya Zhao, Bing Bai, Hai Zhang, Boyang Jason Wu, Changhong Shi
Near-infrared fluorescence (NIRF) dyes have recently emerged as promising tools for non-invasive imaging of different types of cancers. Here, we explored the potential utility of a NIRF DZ-1 dye, with dual imaging and tumour targeting functions, in hepatocellular carcinoma (HCC). We showed the preferential uptake of DZ-1 by HCC cells in vitro and in derived subcutaneous/orthotopic tumour xenografts, accompanied by a minimal effect on normal cells. DZ-1 simplified tumour growth profiling as well, since we were able to correlate NIRF signals with tumour volume and/or tumour-emitting luminescence in mice...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915614/mitochondrial-protein-18-mtp18-plays-a-pro-apoptotic-role-in-chemotherapy-induced-gastric-cancer-cell-apoptosis
#16
Lynn H H Aung, Ruibei Li, Bellur S Prabhakar, Ajay V Maker, Peifeng Li
One of the severe limitations of chemotherapy is the development of drug resistance. However, the mechanisms underlying chemotherapy resistance remain to be elucidated. Mitochondrial mediated apoptosis is a form of cell death induced by chemotherapy. Several chemotherapeutic agents have been shown to induce mitochondrial fission, and finally activate the apoptosis cascade in various cancer cells. Here, we report that the mitochondrial membrane protein 18 (MTP18) induced mitochondrial fragmentation in gastric cancer cells under doxorubicin (DOX) exposure...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28913538/differences-in-cisplatin-distribution-in-sensitive-and-resistant-ovarian-cancer-cells-a-tem-nanosims-study
#17
Ronald F S Lee, Tina Riedel, Stéphane Escrig, Catherine Maclachlan, Graham W Knott, Curt A Davey, Kai Johnsson, Anders Meibom, Paul J Dyson
Cisplatin is a widely used anti-cancer drug, but its effect is often limited by acquired resistance to the compound during treatment. Here, we use a combination of transmission electron microscopy (TEM) and nanoscale-secondary ion mass spectrometry (NanoSIMS) to reveal differences between cisplatin uptake in human ovarian cancers cells, which are known to be susceptible to acquired resistance to cisplatin. Both cisplatin sensitive and resistant cell lines were studied, revealing markedly less cisplatin in the resistant cell line...
September 15, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28913175/regulation-of-endoplasmic-reticulum-mitochondria-ca-2-transfer-and-its-importance-for-anti-cancer-therapies
#18
REVIEW
Gaia Pedriali, Alessandro Rimessi, Luigi Sbano, Carlotta Giorgi, Mariusz R Wieckowski, Maurizio Previati, Paolo Pinton
Inter-organelle membrane contact sites are emerging as major sites for the regulation of intracellular Ca(2+) concentration and distribution. Here, extracellular stimuli operate on a wide array of channels, pumps, and ion exchangers to redistribute intracellular Ca(2+) among several compartments. The resulting highly defined spatial and temporal patterns of Ca(2+) movement can be used to elicit specific cellular responses, including cell proliferation, migration, or death. Plasma membrane (PM) also can directly contact mitochondria and endoplasmic reticulum (ER) through caveolae, small invaginations of the PM that ensure inter-organelle contacts, and can contribute to the regulation of numerous cellular functions through scaffolding proteins such as caveolins...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28910082/macromolecular-profiling-of-organelles-in-normal-diploid-and-cancer-cells
#19
Svitlana M Levchenko, Andrey N Kuzmin, Artem Pliss, Junle Qu, Paras N Prasad
To advance an understanding of cellular regulation and function it is crucial to identify molecular contents in cellular organelles, which accommodate specific biochemical processes. Towards achievement of this goal, we applied micro-Raman-Biomolecular Component Analysis assay for molecular profiling of major organelles in live cells. We used this assay for comparative analysis of proteins 3D conformation and quantification of proteins, RNA and lipids concentrations in nucleoli, endoplasmic reticulum and mitochondria of WI-38 diploid lung fibroblasts and HeLa cancer cells...
September 14, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28903423/mitochondria-sustain-store-operated-currents-in-colon-cancer-cells-but-not-in-normal-colonic-cells-reversal-by-non-steroidal-anti-inflammatory-drugs
#20
Miriam Hernández-Morales, Diego Sobradillo, Ruth A Valero, Eva Muñoz, Daniel Ubierna, Mary P Moyer, Lucía Núñez, Carlos Villalobos
Tumor cells undergo a critical remodeling of intracellular Ca(2+) homeostasis that contribute to important cancer hallmarks. Store-operated Ca(2+) entry (SOCE), a Ca(2+) entry pathway modulated by mitochondria, is dramatically enhanced in colon cancer cells. In addition, most cancer cells display the Warburg effect, a metabolic switch from mitochondrial metabolism to glycolysis that provides survival advantages. Accordingly, we investigated mitochondria control of store-operated currents (SOCs) in two cell lines previously selected for representing human normal colonic cells and colon cancer cells...
August 15, 2017: Oncotarget
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