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https://www.readbyqxmd.com/read/28816773/synergistic-antitumor-effect-of-3-bromopyruvate-and-5-fluorouracil-against-human-colorectal-cancer-through-cell-cycle-arrest-and-induction-of-apoptosis
#1
Dianlong Chong, Linyan Ma, Fang Liu, Zhirui Zhang, Surong Zhao, Qiang Huo, Pei Zhang, Hailun Zheng, Hao Liu
3-Bromopyruvic acid (3-BP) is a well-known inhibitor of energy metabolism. It has been proposed as an anticancer agent as well as a chemosensitizer for use in combination with anticancer drugs. 5-Fluorouracil (5-FU) is the first-line chemotherapeutic agent for colorectal cancer; however, most patients develop resistance to 5-FU through various mechanisms. The aim of this study was to investigate whether 3-BP has a synergistic antitumor effect with 5-FU on human colorectal cancer cells. In our study, combined 3-BP and 5-FU treatment upregulated p53 and p21, whereas cyclin-dependent kinase CDK4 and CDK2 were downregulated, which led to G0/G1 phase arrest...
September 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28816449/paralog-specificity-determines-subcellular-distribution-action-mechanism-and-anticancer-activity-of-trap1-inhibitors
#2
Hye-Kyung Park, Hanbin Jeong, Eunhwa Ko, Geumwoo Lee, Ji-Eun Lee, Sang Kwang Lee, An-Jung Lee, Jin Young Im, Sung Hu, Seong Heon Kim, Ji Hoon Lee, Changwook Lee, Soosung Kang, Byoung Heon Kang
Although Hsp90 inhibitors can inhibit multiple tumorigenic pathways in cancer cells, their anticancer activity has been disappointingly modest. However, by forcing Hsp90 inhibitors into the mitochondria with mitochondrial delivery vehicles, they were converted into potent drugs targeting the mitochondrial Hsp90 paralog TRAP1. Here, to improve mitochondrial drug accumulation without using the mitochondrial delivery vehicle, we increased freely available drug concentrations in the cytoplasm by reducing the binding of the drugs to the abundant cytoplasmic Hsp90...
August 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28815534/alterations-in-ca-2-signalling-via-er-mitochondria-contact-site-remodelling-in-cancer
#3
Martijn Kerkhofs, Carlotta Giorgi, Saverio Marchi, Bruno Seitaj, Jan B Parys, Paolo Pinton, Geert Bultynck, Mart Bittremieux
Inter-organellar contact sites establish microdomains for localised Ca(2+)-signalling events. One of these microdomains is established between the ER and the mitochondria. Importantly, the so-called mitochondria-associated ER membranes (MAMs) contain, besides structural proteins and proteins involved in lipid exchange, several Ca(2+)-transport systems, mediating efficient Ca(2+) transfer from the ER to the mitochondria. These Ca(2+) signals critically control several mitochondrial functions, thereby impacting cell metabolism, cell death and survival, proliferation and migration...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28813136/targeting-of-cellular-organelles-by-fluorescent-plasmid-dna-nanoparticles
#4
Diana Costa, Carolina Costa, Margarida Vaz Caldeira, Luisa Maria Cortes, João A Queiroz, Carla Cruz
The development of a suitable delivery system and the targeting of intracellular organelles are both essential for the success of drug and gene therapies. The conception of fluorescent ligands, displaying targeting specificity together with low toxicity, is an emerging and reliable tool to develop innovative delivery systems. Biocompatible BSA or pDNA/ligand nanoparticles were synthesized by a co-precipitation method and were shown to display adequate sizes and morphology for delivery purposes, and positive surface charges...
August 16, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28812748/cyclometalated-iridium-iii-n-heterocyclic-carbene-complexes-as-potential-mitochondrial-anticancer-and-photodynamic-agents
#5
Yi Li, Bing Liu, Xin-Ran Lu, Meng-Feng Li, Liang-Nian Ji, Zong-Wan Mao
Metal N-heterocyclic carbene (NHC) complexes represent a promising class of anticancer therapeutic agents. In this work, four cyclometalated iridium(iii) complexes (Ir1-Ir4) containing N-heterocyclic carbene ligands have been explored as mitochondrial anticancer and photodynamic agents. These complexes are more cytotoxic than cisplatin against the cancer cells screened, can quickly penetrate into A549 cells and are mainly localized in the mitochondria. Mechanism studies show that these complexes exert their anticancer efficacy by increasing the intracellular ROS level, reducing the mitochondrial membrane potential (MMP) and inducing apoptosis...
August 16, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28812582/control-of-intestinal-stem-cell-function-and-proliferation-by-mitochondrial-pyruvate-metabolism
#6
John C Schell, Dona R Wisidagama, Claire Bensard, Helong Zhao, Peng Wei, Jason Tanner, Aimee Flores, Jeffrey Mohlman, Lise K Sorensen, Christian S Earl, Kristofor A Olson, Ren Miao, T Cameron Waller, Don Delker, Priyanka Kanth, Lei Jiang, Ralph J DeBerardinis, Mary P Bronner, Dean Y Li, James E Cox, Heather R Christofk, William E Lowry, Carl S Thummel, Jared Rutter
Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation...
August 14, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28811338/emerging-functions-of-the-fanconi-anemia-pathway-at-a-glance
#7
REVIEW
Rhea Sumpter, Beth Levine
Fanconi anemia (FA) is a rare disease, in which homozygous or compound heterozygous inactivating mutations in any of 21 genes lead to genomic instability, early-onset bone marrow failure and increased cancer risk. The FA pathway is essential for DNA damage response (DDR) to DNA interstrand crosslinks. However, proteins of the FA pathway have additional cytoprotective functions that may be independent of DDR. We have shown that many FA proteins participate in the selective autophagy pathway that is required for the destruction of unwanted intracellular constituents...
August 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28811220/euphorbia-lunulata-extract-acts-on-multidrug-resistant-gastric-cancer-cells-to-inhibit-cell-proliferation-migration-and-invasion-arrest-cell-cycle-progression-and-induce-apoptosis
#8
Zhaoying Fu, Xiaodong Han, Juan Du, Xiaoxiao Han, Weipeng Liu, Shumei Shao, Xiaobin Liu
ETHNOPHARMACOLOGICAL RELEVANCE: The milky sap or the aboveground part of the plant Euphorbia lunulata has long been used by Chinese people to treat noncancerous growths and cancerous ailments but the specific mode of action and the action mechanism remain to be elucidated. AIM OF THE STUDY: To investigate the effects of Euphorbia lunulata extract on cell proliferation, migration, invasion, cell cycle progression, and apoptosis of multidrug resistant human gastric cancer cells; To study the mechanism of apoptosis induction by Euphorbia lunulata extract in multidrug resistant human gastric cancer cells...
August 12, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28808415/foxo-signaling-pathways-as-therapeutic-targets-in-cancer
#9
REVIEW
Mohd Farhan, Haitao Wang, Uma Gaur, Peter J Little, Jiangping Xu, Wenhua Zheng
Many transcription factors play a key role in cellular differentiation and the delineation of cell phenotype. Transcription factors are regulated by phosphorylation, ubiquitination, acetylation/deacetylation and interactions between two or more proteins controlling multiple signaling pathways. These pathways regulate different physiological processes and pathological events, such as cancer and other diseases. The Forkhead box O (FOXO) is one subfamily of the fork head transcription factor family with important roles in cell fate decisions and this subfamily is also suggested to play a pivotal functional role as a tumor suppressor in a wide range of cancers...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28807721/selenopheno-quinolinones-and-coumarins-promote-cancer-cell-apoptosis-by-ros-depletion-and-caspase-7-activation
#10
Ilona Domracheva, Iveta Kanepe-Lapsa, Ludmila Jackevica, Jelena Vasiljeva, Pavel Arsenyan
AIM: This study was designed to investigate the mechanism underlying cancer cell apoptosis caused by selenophenoquinolinones and coumarins. MATERIALS AND METHODS: Twelve derivatives were studied according to their ability to suppress the proliferation of cancer cells in vitro (i.e., HepG2, MH-22A, MCF-7), induce cell apoptosis, modulate cellular antioxidant enzyme system activities (i.e., SOD, GPx, TrxR), influence the level of ROS, and modulate caspase activity...
August 11, 2017: Life Sciences
https://www.readbyqxmd.com/read/28807237/mitochondrial-dysfunctions-in-bladder-cancer-exploring-their-role-as-disease-markers-and-potential-therapeutic-targets
#11
REVIEW
Antonella Cormio, Francesca Sanguedolce, Clara Musicco, Vito Pesce, Giuseppe Calò, Pantaleo Bufo, Giuseppe Carrieri, Luigi Cormio
Bladder cancer (BC) is a major cause of mortality worldwide as it currently lacks fully reliable markers of disease outcome and effective molecular targets for therapy. Mitochondria play a key role in cell metabolism but the role of mitochondrial dysfunctions in BC has been scarcely investigated. In this review, we explored current evidence for the potential role of mitochondrial DNA (mtDNA) alterations (point mutations and copy number) as disease markers in BC. Some germline mtDNA mutations detectable in blood could represent a non-invasive tool to predict the risk of developing BC...
September 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28799020/from-discovery-of-the-chop-axis-and-targeting-clpp-to-the-identification-of-additional-axes-of-the-uprmt-driven-by-the-estrogen-receptor-and-sirt3
#12
Timothy C Kenny, Doris Germain
The mitochondrial UPR (UPR(mt)) is rapidly gaining attention. While most studies on the UPR(mt) have focused on its role in aging, emerging studies suggest an important role of the UPR(mt) in cancer. Further, several of the players of the UPR(mt) in mammalian cells have well reported roles in the maintenance of the organelle. The goal of this review is to emphasize aspects of the UPR(mt) that have been overlooked in the current literature, describe the role of specific players of the UPR(mt) in the biology of the mitochondria and highlight the intriguing possibility that targeting the UPR(mt) in cancer may be already within reach...
August 10, 2017: Journal of Bioenergetics and Biomembranes
https://www.readbyqxmd.com/read/28798902/the-mitochondrial-unfolded-protein-response-as-a-non-oncogene-addiction-to-support-adaptation-to-stress-during-transformation-in-cancer-and-beyond
#13
REVIEW
Timothy C Kenny, Giovanni Manfredi, Doris Germain
Upon accumulation of misfolded proteins in the mitochondria, the mitochondrial unfolded protein response (UPR(mt)) is activated. This review focuses on the role of this response in cancer. We discuss evidence that during transformation, the UPR(mt) may play an essential role in the maintenance of the integrity of the mitochondria in the face of increased oxidative stress. However, the role of the UPR(mt) in other diseases is also emerging and is therefore also briefly discussed.
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28798402/nutlin-3-enhances-the-bortezomib-sensitivity-of-p53-defective-cancer-cells-by-inducing-paraptosis
#14
Dong Min Lee, In Young Kim, Min Ji Seo, Mi Ri Kwon, Kyeong Sook Choi
The proteasome inhibitor, bortezomib, is ineffective against many solid tumors. Nutlin-3 is a potent antagonist of human homolog of murine double minute 2/p53 interaction exhibiting promising therapeutic anti-cancer activity. In this study, we show that treatment of various p53-defective bortezomib-resistant solid tumor cells with bortezomib plus nutlin-3 induces paraptosis, which is a cell death mode accompanied by dilation of the endoplasmic reticulum (ER) and mitochondria. Bortezomib alone did not markedly alter cellular morphology, and nutlin-3 alone induced only a transient mitochondrial dilation...
August 11, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28795798/a-two-photon-and-deep-red-emission-ratiometric-fluorescent-probe-with-a-large-emission-shift-and-signal-ratios-for-sulfur-dioxide-ultrafast-response-and-applications-in-living-cells-brain-tissues-and-zebrafishes
#15
Yanyan Ma, Yonghe Tang, Yuping Zhao, Shiying Gao, Weiying Lin
Sulfur dioxide (SO2) is a dangerous environmental pollutant. Excessive intake of it may cause some respiratory diseases and even lung cancer. The development of effective methods for detecting of SO2 is of great importance for environment and physiology. Herein, we have designed and synthesized a novel two-photon (TP) and deep-red emission ratiometric fluo-rescent probe (CP) for detecting of SO2. Notably, the novel probe CP exhibited ultrafast response to SO2 in less than 5 sec-onds, and displayed a great emission shift (195 nm) and a large emission signal ratio variation (enhancement from 0...
August 10, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28795692/the-novel-resveratrol-derivative-3-5-diethoxy-3-4-dihydroxy-trans-stilbene-induces-mitochondrial-ros-mediated-er-stress-and-cell-death-in-human-hepatoma-cells-in-vitro
#16
Jae-Woo Park, Woo-Gyun Choi, Phil-Jun Lee, Su-Wol Chung, Byung-Sam Kim, Hun-Taeg Chung, Sungchan Cho, Jong-Heon Kim, Byoung-Heon Kang, Hyoungsu Kim, Hong-Pyo Kim, Sung-Hoon Back
Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a well-known polyphenol that is present in grapes, peanuts, pine seeds, and several other plants. Resveratrol exerts deleterious effects on various types of human cancer cells. Here, we analyzed the cell death-inducing mechanisms of resveratrol-006 (Res-006), a novel resveratrol derivative in human liver cancer cells in vitro. Res-006 was more effectively suppressed the viability of HepG2 human hepatoma cells than resveratrol (the IC50 values were 67.2 and 354...
August 10, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28791837/the-role-of-17%C3%AE-estradiol-metabolites-in-chromium-induced-oxidative-stress
#17
Ewa Sawicka, Anna Długosz
BACKGROUND: The increasing incidence of estrogen-dependent breast cancer and the presence in the environment of a large number of factors that interact with estrogen receptors have sparked interest in chemical influences on estrogen-dependent processes. In a previous work, the authors examined the interaction of estradiol with chromium. In the present article the importance of estradiol biotransformation in these interactions is investigated. There is no information in the available literature about the role of metabolites in exposure to chromium...
March 2017: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/28791416/luteolin-induces-apoptotic-cell-death-via-antioxidant-activity-in-human-colon-cancer-cells
#18
Kyoung Ah Kang, Mei Jing Piao, Yea Seong Ryu, Yu Jae Hyun, Jeong Eon Park, Kristina Shilnikova, Ao Xuan Zhen, Hee Kyoung Kang, Young Sang Koh, Yong Joo Jeong, Jin Won Hyun
The present study determined whether luteolin induces HT-29 colon cancer cell death through an antioxidant effect such as the activation of antioxidant enzymes. Luteolin decreased cell viability in human colon cancer cells (HT-29), whereas it had no effect on normal colon cells (FHC). Luteolin induced apoptosis by activating the mitochondria-mediated caspase pathway in HT-29 cells. Luteolin caused loss of the mitochondrial membrane action potential, increased mitochondrial Ca2+ level, upregulated Bax, downregulated Bcl-2, induced the release of cytochrome c from mitochondria to the cytosol, and increased the levels of the active forms of caspase-9 and caspase-3...
August 2, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28783712/machine-learning-for-predicting-lifespan-extending-chemical-compounds
#19
Diogo G Barardo, Danielle Newby, Daniel Thornton, Taravat Ghafourian, João Pedro de Magalhães, Alex A Freitas
Increasing age is a risk factor for many diseases; therefore developing pharmacological interventions that slow down ageing and consequently postpone the onset of many age-related diseases is highly desirable. In this work we analyse data from the DrugAge database, which contains chemical compounds and their effect on the lifespan of model organisms. Predictive models were built using the machine learning method random forests to predict whether or not a chemical compound will increase Caenorhabditis elegans' lifespan, using as features Gene Ontology (GO) terms annotated for proteins targeted by the compounds and chemical descriptors calculated from each compound's chemical structure...
July 18, 2017: Aging
https://www.readbyqxmd.com/read/28783605/a-series-of-terpyridine-containing-flexible-amino-diethylacetate-derivatives-with-large-two-photon-action-cross-sections-for-effective-mitochondrial-imaging-in-living-liver-cancerous-cells
#20
Ran Jia, Yingying Zhu, Lei Hu, Qiru Xiong, Meng Zhao, Mingzhu Zhang, Xiaohe Tian
Small molecules possess large two-photon action cross sections (Φσ) are highly demanded for biological purpose. Herein, three novel terpyridine containing flexible amino diethylacetate organic small molecules (A1, A2 and A3) were rationally designed and their photophysical properties were investigated both experimentally and theoretically. The results revealed that the three chromophores possess large Φσ and remarkable Stokes' shift in high polar solvents, which are particularly benefit for further biological imaging application...
July 31, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
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