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https://www.readbyqxmd.com/read/28222492/discovery-of-mieap-regulated-mitochondrial-quality-control-as-a-new-function-of-tumor-suppressor-p53
#1
REVIEW
Yasuyuki Nakamura, Hirofumi Arakawa
The tumor suppressor p53 gene is frequently mutated in human cancers, and the p53 protein suppresses cancer. However, the mechanism behind the p53-mediated tumor suppression is still unclear. Recently, Mieap (the mitochondria-eating protein) was identified as a p53-inducible protein. Mieap induces the accumulation of lysosomal proteins within mitochondria (MALM: Mieap-induced accumulation of lysosome-like organelles within mitochondria) in response to mitochondrial damage, and eliminates the oxidized mitochondrial proteins to repair unhealthy mitochondria...
February 21, 2017: Cancer Science
https://www.readbyqxmd.com/read/28220885/cancer-cell-mitochondria-targeting-by-pancratistatin-analogs-is-dependent-on-functional-complex-ii-and-iii
#2
Dennis Ma, Christopher Pignanelli, Daniel Tarade, Tyler Gilbert, Megan Noel, Fadi Mansour, Scott Adams, Alexander Dowhayko, Kyle Stokes, Sergey Vshyvenko, Tomas Hudlicky, James McNulty, Siyaram Pandey
Enhanced mitochondrial stability and decreased dependence on oxidative phosphorylation confer an acquired resistance to apoptosis in cancer cells, but may present opportunities for therapeutic intervention. The compound pancratistatin (PST) has been shown to selectively induce apoptosis in cancer cells. However, its low availability in nature has hindered its clinical advancement. We synthesized PST analogs and a medium-throughput screen was completed. Analogs SVTH-7, -6, and -5 demonstrated potent anti-cancer activity greater than PST and several standard chemotherapeutics...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220193/hsa-mir-4485-regulates-mitochondrial-functions-and-inhibits-the-tumorigenicity-of-breast-cancer-cells
#3
Lakshmi Sripada, Kritarth Singh, Anastasiya V Lipatova, Aru Singh, Paresh Prajapati, Dhanendra Tomar, Khyati Bhatelia, Milton Roy, Rochika Singh, Madan M Godbole, Peter M Chumakov, Rajesh Singh
The modulation of mitochondrial functions is important for maintaining cellular homeostasis. Mitochondria essentially depend on the import of RNAs and proteins encoded by the nuclear genome. MicroRNAs encoded in the nucleus can translocate to mitochondria and target the genome, affecting mitochondrial function. Here, we analyzed the role of miR-4485 in the regulation of mitochondrial functions. We showed that miR-4485 translocated to mitochondria where its levels varied in response to different stress conditions...
February 20, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28219737/membrane-androgen-receptor-characteristics-of-human-zip9-slc39a-zinc-transporter-in-prostate-cancer-cells-androgen-specific-activation-and-involvement-of-an-inhibitory-g-protein-in-zinc-and-map-kinase-signaling
#4
Peter Thomas, Yefei Pang, Jing Dong
Characteristics of novel human membrane androgen receptor (mAR), ZIP9 (SLC39A9), were investigated in ZIP9-transfected PC-3 cells (PC3-ZIP9). Ligand blot analysis showed plasma membrane [(3)H]-T binding corresponds to the position of ZIP9 on Western blots which suggests ZIP9 can bind [(3)H]-T alone, without a protein partner. Progesterone antagonized testosterone actions, blocking increases in zinc, Erk phosphorylation and apoptosis, further evidence that ZIP9 is specifically activated by androgens. Pre-treatment with GTPγS and pertussis toxin decreased plasma membrane [(3)H]-T binding and blocked testosterone-induced increases in Erk phosphorylation and intracellular zinc, indicating ZIP9 is coupled to an inhibitory G protein (Gi) that mediates both MAP kinase and zinc signaling...
February 17, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28219123/identification-of-core-gene-networks-and-hub-genes-associated-with-progression-of-nonalcoholic-fatty-liver-disease-by-rna-sequencing
#5
Kikuko Hotta, Masataka Kikuchi, Takuya Kitamoto, Aya Kitamoto, Yuji Ogawa, Yasushi Honda, Takaomi Kessoku, Kaori Kobayashi, Masato Yoneda, Kento Imajo, Wataru Tomeno, Akihiro Nakaya, Yutaka Suzuki, Satoru Saito, Atsushi Nakajima
AIM: Nonalcoholic fatty liver disease (NAFLD) progresses because of the interaction between numerous genes. Thus, we performed weighted gene co-expression network analysis to identify core gene networks and key genes associated with NAFLD progression. METHODS: We enrolled 39 patients with mild NAFLD (fibrosis stages 0 to 2) and 21 with advanced NAFLD (fibrosis stages 3 or 4). Total RNA was extracted from frozen liver biopsies, and sequenced to capture a large dynamic range of expression levels...
February 20, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28215509/triphenylphosphonium-modified-poly-ethylene-glycol-poly-%C3%AE%C2%B5-caprolactone-micelles-for-mitochondria-targeted-gambogic-acid-delivery
#6
Yingqi Xu, Shengpeng Wang, Hon Fai Chan, Yuling Liu, Hui Li, Chengwei He, Zeyong Li, Meiwan Chen
Mitochondria are important targets for the intracellular delivery of drugs and DNA. For mitochondria-targeted delivery, a mitochondriotropic molecule, triphenylphosphonium (TPP), was applied to the synthesis of amphiphilic TPP-poly(ethylene glycol)-poly(ε-caprolactone) (TPP-PEG-PCL) polymers. The TPP-PEG-PCL polymer was used to prepare micelles using a solvent evaporation method for the delivery of gambogic acid (GA) (GA-TPP). The micelles were obtained with a favorable particle size of 150.07±11.71nm and an encapsulation efficiency of 80...
February 12, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28214549/atp-dependent-activity-and-mitochondrial-localization-of-drug-efflux-pumps-in-doxorubicin-resistant-breast-cancer-cells
#7
Julie Dartier, Elsa Lemaitre, Igor Chourpa, Caroline Goupille, Stéphane Servais, Stéphan Chevalier, Karine Mahéo, Jean-François Dumas
BACKGROUND: We hypothesized that, among the mechanisms of drug-resistance acquired by doxorubicin (DOX)-resistant breast cancer cells to maintain cell survival, ATP-dependent drug efflux pumps could be expressed in their mitochondrial membranes and this might limit the accumulation of DOX in this subcellular compartment in relation to mitochondrial ATP production. Methods/results Mitochondrial DOX accumulation: the presence and the activity of mitochondrial efflux pumps and their relationship with mitochondrial ATP synthesis were analyzed in DOX-resistant (MCF-7dox(R)) and -sensitive (MCF-7(S)) breast cancer cells...
February 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28214344/neferine-potentiates-the-antitumor-effect-of-cisplatin-in-human-lung-adenocarcinoma-cells-via-a-mitochondria-mediated-apoptosis-pathway
#8
Kalai Selvi Sivalingam, Poornima Paramasivan, Ching Feng Weng, Viswanadha Vijaya Padma
Cisplatin is one of the most potent chemotherapeutic agents for the treatment of many types of solid tumors but its efficacy is often limited by the development of resistance and dose limiting toxicity. Neferine is an alkaloid isolated from seed embryo of Nelumbo nucifera, it has recently been shown to have anticancer effects in various human cancer cell lines. The present investigation is designed to study the chemosensitizing ability of neferine with cisplatin in A549 cells. Neferine potentiates the cisplatin induced apoptosis through the exploration of characteristic apoptotic morphological changes, induced sub-G0/G1 cell cycle arrest, ROS hypergeneration, significant loss of cellular antioxidant enzymes as well as loss of mitochondrial membrane potential (ΔΨM)...
February 18, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28213961/chrysin-induces-death-of-prostate-cancer-cells-by-inducing-ros-and-er-stress
#9
Soomin Ryu, Whasun Lim, Fuller W Bazer, Gwonhwa Song
Chrysin is a natural flavone found in numerous plant extracts, honey and propolis that has multiple biological activities including anti-cancer effects. Understanding of biological mechanisms mediated in response to chrysin in cancerous cells may provide novel insight into chemotherapeutic approaches with reduced side effects in cancers. In the present study, we investigated functional roles of chrysin in progression of prostate cancer cells using DU145 and PC-3 cell lines. The results showed that chrysin induced apoptosis of cells evidenced by DNA fragmentation and increasing the population of both DU145 and PC-3 cells in the sub-G1 phase of the cell cycle...
February 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28213331/mitochondrial-metabolism-and-energy-sensing-in-tumor-progression
#10
REVIEW
Luisa Iommarini, Anna Ghelli, Giuseppe Gasparre, Anna Maria Porcelli
Energy homeostasis is pivotal for cell fate since metabolic regulation, cell proliferation and death are strongly dependent on the balance between catabolic and anabolic pathways. In particular, metabolic and energetic changes have been observed in cancer cells even before the discovery of oncogenes and tumor suppressors, but has been neglected for a long time. Instead, during the past 20years a renaissance of the study of tumor metabolism has led to a revised and more accurate sight of the metabolic landscape of cancer cells...
February 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28213330/drug-discovery-strategies-in-the-field-of-tumor-energy-metabolism-limitations-by-metabolic-flexibility-and-metabolic-resistance-to-chemotherapy
#11
REVIEW
N D Amoedo, E Obre, R Rossignol
The search for new drugs capable of blocking the metabolic vulnerabilities of human tumors has now entered the clinical evaluation stage, but several projects already failed in phase I or phase II. In particular, very promising in vitro studies could not be translated in vivo at preclinical stage and beyond. This was the case for most glycolysis inhibitors that demonstrated systemic toxicity. A more recent example is the inhibition of glutamine catabolism in lung adenocarcinoma that failed in vivo despite a strong addiction of several cancer cell lines to glutamine in vitro...
February 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28212731/hamlet-a-protein-lipid-complex-with-broad-tumoricidal-activity
#12
REVIEW
James C S Ho, Aftab Nadeem, Catharina Svanborg
HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is a tumoricidal protein-lipid complex with broad effects against cancer cells of different origin. The therapeutic potential is emphasized by a high degree of specificity for tumor tissue. Here we review early studies of HAMLET, in collaboration with the Orrenius laboratory, and some key features of the subsequent development of the HAMLET project. The early studies focused on the apoptotic response that accompanies death in HAMLET treated tumor cells and the role of mitochondria in this process...
January 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28212727/mitophagy-link-to-cancer-development-and-therapy
#13
REVIEW
Andrey V Kulikov, Ekaterina A Luchkina, Vladimir Gogvadze, Boris Zhivotovsky
Mitophagy, the selective degradation of mitochondria via the autophagic pathway, is a vital mechanism of mitochondrial quality control in cells. Mitophagy is responsible for the removal of malfunctioning or damaged mitochondria, which is essential for normal cellular physiology and tissue development. Pathways involved in the regulation of mitophagy, tumorigenesis, and cell death are overlapping in many cases and may be triggered by common upstream signals, which converge at the mitochondria. The failure to properly modulate mitochondrial turnover in response to oncogenic stresses can either stimulate or suppress tumorigenesis...
January 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28209723/functional-metabolic-and-dynamic-mitochondrial-changes-in-the-rat-cirrhosis-hepatocellular-carcinoma-model-and-the-protective-effect-of-ifc-305
#14
Enrique Chavez, Maria Guadalupe Lozano-Rosas, Mariana Dominguez-Lopez, Gabriela Velasco-Loyden, Jesus Rafael Rodriguez-Aguilera, Concepcion Jose-Nunez, Marietta Tuena de Gomez-Puyou, Victoria Chagoya de Sanchez
BACKGROUND: Mitochondrion is an important metabolic and energetic organelle which regulates several cellular processes. Mitochondrial dysfunction has been related with liver diseases including hepatocellular carcinoma. As a result, the energetic demand is not properly supplied and mitochondrial morphologic changes has been observed resulting in an altered metabolism. We previously demonstrated the chemopreventive effect of the hepatoprotector IFC-305. AIM: In this work we aimed to evaluate the functional, metabolic, and dynamic mitochondrial alterations in the sequential model of cirrhosis-hepatocellular carcinoma induced by diethylnitrosamine in rats and the possible beneficial effect of IFC-305...
February 16, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28209717/autophagy-metabolism-and-cancer
#15
Jessie Yanxiang Guo, Eileen White
Macroautophagy (autophagy hereafter) is a process that collects cytoplasmic components, particularly mitochondria, and degrades them in lysosomes. In mammalian systems, basal autophagy levels are normally low but are profoundly stimulated by starvation and essential for survival. Cancer cells up-regulate autophagy and can be more autophagy-dependent than most normal tissues. Genetic deficiency in essential autophagy genes in tumors in many autochthonous mouse models for cancer reduces tumor growth. In K-ras(G12D)-driven non-small cell lung cancer (NSCLC) and other models, autophagy sustains metabolism and survival...
February 16, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28208702/the-glutamate-dehydrogenase-pathway-and-its-roles-in-cell-and-tissue-biology-in-health-and-disease
#16
REVIEW
Andreas Plaitakis, Ester Kalef-Ezra, Dimitra Kotzamani, Ioannis Zaganas, Cleanthe Spanaki
Glutamate dehydrogenase (GDH) is a hexameric enzyme that catalyzes the reversible conversion of glutamate to α-ketoglutarate and ammonia while reducing NAD(P)⁺ to NAD(P)H. It is found in all living organisms serving both catabolic and anabolic reactions. In mammalian tissues, oxidative deamination of glutamate via GDH generates α-ketoglutarate, which is metabolized by the Krebs cycle, leading to the synthesis of ATP. In addition, the GDH pathway is linked to diverse cellular processes, including ammonia metabolism, acid-base equilibrium, redox homeostasis (via formation of fumarate), lipid biosynthesis (via oxidative generation of citrate), and lactate production...
February 8, 2017: Biology
https://www.readbyqxmd.com/read/28206987/id2-promotes-survival-of-glioblastoma-cells-during-metabolic-stress-by-regulating-mitochondrial-function
#17
Zhonghua Zhang, Gilbert J Rahme, Pranam D Chatterjee, Matthew C Havrda, Mark A Israel
Tumor cells proliferate in cellular environments characterized by a lack of optimal tissue organization resulting oftentimes in compromised cellular metabolism affecting nutrition, respiration, and energetics. The response of tumor cells to adverse environmental conditions is a key feature affecting their pathogenicity. We found that inhibitor of DNA binding 2 (ID2) expression levels significantly correlate with the ability of glioblastoma (GBM)-derived cell lines to survive glucose deprivation. ID2 suppressed mitochondrial oxidative respiration and mitochondrial ATP production by regulating the function of mitochondrial electron transport chain (mETC) complexes, resulting in reduced superoxide and reactive oxygen species (ROS) production from mitochondria...
February 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28205173/measurement-of-mitochondrial-cholesterol-import-using-a-mitochondria-targeted-cyp11a1-fusion-construct
#18
Barry E Kennedy, Mark Charman, Barbara Karten
All animal membranes require cholesterol as an essential regulator of biophysical properties and function, but the levels of cholesterol vary widely among different subcellular compartments. Mitochondria, and in particular the inner mitochondrial membrane, have the lowest levels of cholesterol in the cell. Nevertheless, mitochondria need cholesterol for membrane maintenance and biogenesis, as well as oxysterol, steroid, and hepatic bile acid production. Alterations in mitochondrial cholesterol have been associated with a range of pathological conditions, including cancer, hepatosteatosis, cardiac ischemia, Alzheimer's, and Niemann-Pick Type C Disease...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28198103/synthesis-of-5%C3%AE-8%C3%AE-ergosterol-peroxide-3-carbamate-derivatives-and-fluorescent-mitochondria-targeting-conjugate-for-enhanced-anticancer-activities
#19
Ming Bu, Tingting Cao, Hongxia Li, Mingzhou Guo, Burton B Yang, Chengchu Zeng, Liming Hu
By inspiration of significant anticancer activity of our previously screened natural ergosterol peroxide (1), a series of novel ergosterol peroxide 3-carbamate derivatives were synthesized and characterized. The anti-proliferative activity of synthesized compounds against human hepatocellular carcinoma cells (HepG2, SK-Hep1) and human breast cancer cells (MCF-7, MDA-MB231) were investigated. Compound 3d, 3f and their hydrochloride exhibited significant in vitro anti-proliferative activity against the tested tumor cell lines, with IC50 values ranging from 0...
February 15, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28197625/different-effect-of-resveratrol-to-induction-of-apoptosis-depending-on-the-type-of-human-cancer-cells
#20
Michinori Takashina, Sayaka Inoue, Kei Tomihara, Kengo Tomita, Kohshi Hattori, Qing-Li Zhao, Tokiko Suzuki, Makoto Noguchi, Wakana Ohashi, Yuichi Hattori
The effect of resveratrol on various human cancer cells was investigated with special focus on apoptotic cell death, in an attempt to further characterize its mechanism of action. There were great differences in the anti-viability effect of resveratrol between different types of human cancer cells. While the inhibition of cell viability by resveratrol was marked in U937 and MOLT-4 leukemia cells, resveratrol moderately inhibited cell viability in MCF-7 breast, HepG2 liver, and A549 lung cancer cells, and the effect was slight on cell viability in Caco-2, HCT116, and SW480 colon cancer cells...
March 2017: International Journal of Oncology
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