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Mitochondria Cancer

Paul S Jeng, Akane Inoue-Yamauchi, James J Hsieh, Emily H Cheng
Mitochondria play key roles in mammalian apoptosis, a highly regulated genetic program of cell suicide. Multiple apoptotic signals culminate in mitochondrial outer membrane permeabilization (MOMP), which not only couples the mitochondria to the activation of caspases but also initiates caspase-independent mitochondrial dysfunction. The BCL-2 family proteins are central regulators of MOMP. Multidomain pro-apoptotic BAX and BAK are essential effectors responsible for MOMP, whereas anti-apoptotic BCL-2, BCL-XL , and MCL-1 preserve mitochondrial integrity...
June 2018: Current Opinion in Physiology
Emil Lou, Edward Zhai, Akshat Sarkari, Snider Desir, Phillip Wong, Yoshie Iizuka, Jianbo Yang, Subbaya Subramanian, James McCarthy, Martina Bazzaro, Clifford J Steer
Intercellular communication is vital to the ecosystem of cancer cell organization and invasion. Identification of key cellular cargo and their varied modes of transport are important considerations in understanding the basic mechanisms of cancer cell growth. Gap junctions, exosomes, and apoptotic bodies play key roles as physical modalities in mediating intercellular transport. Tunneling nanotubes (TNTs)-narrow actin-based cytoplasmic extensions-are unique structures that facilitate direct, long distance cell-to-cell transport of cargo, including microRNAs, mitochondria, and a variety of other sub cellular components...
2018: Frontiers in Cell and Developmental Biology
Margherita Protasoni, Albert M Kroon, Jan-Willem Taanman
Tetracyclines have anticancer properties in addition to their well-known antibacterial properties. It has been proposed that tetracyclines slow metastasis and angiogenesis through inhibition of matrix metalloproteinases. However, we believe that the anticancer effect of tetracyclines is due to their inhibition of mitochondrial protein synthesis, resulting in a decrease of the mitochondrial energy generating capacity. Several groups have developed analogs that are void of antibacterial action. An example is COL-3, which is currently tested for its anticancer effects in clinical trials...
September 18, 2018: Oncotarget
Kaiyuan Ni, Guangxu Lan, Samuel S Veroneau, Xiaopin Duan, Yang Song, Wenbin Lin
Selective delivery of photosensitizers to mitochondria of cancer cells can enhance the efficacy of photodynamic therapy (PDT). Though cationic Ru-based photosensitizers accumulate in mitochondria, they require excitation with less penetrating short-wavelength photons, limiting their application in PDT. We recently discovered X-ray based cancer therapy by nanoscale metal-organic frameworks (nMOFs) via enhancing radiotherapy (RT) and enabling radiodynamic therapy (RDT). Herein we report Hf-DBB-Ru as a mitochondria-targeted nMOF for RT-RDT...
October 17, 2018: Nature Communications
Adam J Smith, Peter J Gawne, Michelle T Ma, Philip J Blower, Richard Southworth, Nicholas J Long
Radiolabelled lipophilic cations that accumulate in mitochondria according to the magnitude of the mitochondrial membrane potential can be used to report non-invasively on mitochondrial dysfunction in cardiovascular disease, cardiotoxicity, and cancer. While several such cations are already commercially available for SPECT imaging, PET offers greater promise in terms of sensitivity, resolution, and capacity for dynamic imaging and pharmacokinetic modelling. We have therefore synthesised a series of three triarylphosphonium-functionalised DO3A chelators for positron emitter gallium-68, with differing alkyl-functionalisation motifs to provide opportunities for tunable lipophilicity as a means of optimising their pharmacokinetics...
October 17, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
Minghui Chang, Xingguo Song, Xinran Geng, Xingwu Wang, Weijun Wang, Thomas C Chen, Li Xie, Xianrang Song
BACKGROUND: Temozolomide-perillyl alcohol conjugate (TMZ-POH), a novel Temozolomide (TMZ) analog developed based on the conjugation of TMZ and perillyl alcohol (POH), displayed strong anticancer potency in multiple cancer types. In this study, we aimed to clarify the relationship between TMZ-POH and autophagy, and explore the underlying mechanisms involved in. METHODS: The proteins involved in autophagy, mitochondrial fission, lysosomal function and membrane traffic were detected by western blots; Autophagosome, mitochondria and lysosome were visualized by transmission electron microscope (TEM) and immunostaining; Apoptosis analysis and fluorescence probe detection were applied by flow cytometry...
October 16, 2018: Journal of Experimental & Clinical Cancer Research: CR
Julie A MacDonald, Niharika Kura, Carleigh Sussman, Dori C Woods
BACKGROUND: Cellular metabolic changes that accompany malignant transformation have been heralded as hallmark features of cancer. However, metabolic signatures between neoplasms can be unique, allowing for distinctions in malignancy, invasion and chemoresistance between cancer types and subtypes. Mitochondria are central metabolic mediators, as cellular bioenergetics veers from oxidative phosphorylation to glycolysis. Herein, we evaluate the role of mitochondria in maintenance of cellular metabolism, proliferation, and survival in the adult granulosa tumor cell line, KGN, as well as three epithelial ovarian cancer cell lines to determine distinctions in specific features...
October 16, 2018: Journal of Ovarian Research
Seyithan Taysi, Ayse Saglam Tascan, Mete Gurol Uuro, Mustafa Demir
Oxygen is used by eukaryotic cells for metabolic transformations and energy production in mitochondria. Under physiological conditions, there is a constant endogenous production of free radicals that interact as signaling molecules in physiological mechanisms. Free radicals are neutral molecules, which are produced by separation of ions and molecules. In regular conditions production and disposal of free radicals are at equilibrium. However this equilibrium may not always be experienced, where these species are not eliminated by antioxidants or are excessively produced...
October 15, 2018: Mini Reviews in Medicinal Chemistry
Wang Wang, Jibing Wu, Qingyan Zhang, Xue Li, Xixi Zhu, Qiuying Wang, Shasha Cao, Linfang Du
Lung cancer is the main health threat in the world. Recently, oleuropein has been reported to have potent antioxidant and anticancer activities. However, the antitumor effects of oleuropein on H1299 cells are not well understood. Therefore, the purpose of this paper is tantamount to explore the effects of oleuropein on H1299 cells and its underlying mechanism that may be involved. Oleuropein treatment in H1299 cells resulted in cell cycle distribution at G2 /M arrest and apoptosis in a dose-dependent manner...
October 15, 2018: Journal of Cellular Biochemistry
Sheng-Song Chen, Xiao-Yun Tu, Li-Xia Xie, Lv-Ping Xiong, Juan Song, Xiao-Qun Ye
Acquired resistance to chemotherapy is a major limitation for the successful treatment of lung cancer. Previously, we and others showed that formation of tumor spheres is associated with chemotherapy resistance in lung cancer cells, but the underlying mechanisms remained largely unknown. In the current study, we show that mitochondrial activity is significantly higher in A549 tumor spheres versus monolayer cells, establishing mitochondria as a putative target for antitumor therapy. To this end, we designed a peptide nucleic acids (PNAs) coupled with triphenylphosphonium (TPP) to target the displacement loop (D-loop) regulatory region of mitochondrial DNA (PNA-mito)...
2018: American Journal of Translational Research
Iru Paudel, Sean M Hernandez, Gilda M Portalatin, Tara P Chambers, Jeremy W Chambers
The occurrence of chemotherapy-resistant tumors makes ovarian cancer (OC) the most lethal gynecological malignancy. While many factors may contribute to chemoresistance, the mechanisms responsible for regulating tumor vulnerability are under investigation. Our analysis of gene expression data revealed that Sab, a mitochondrial outer membrane (MOM) scaffold protein, was down-regulated in OC patients. Sab-mediated signaling induces cell death suggesting that this apoptotic pathway is diminished in OC.  We examined Sab expression in a panel of OC cell lines and found that the magnitude of Sab expression correlated to chemo-responsiveness; wherein, OC cells with low Sab levels were chemoresistant...
October 15, 2018: Biochemical Journal
Özge Rencüzoğullari, Elif Damla Arısan, Pinar Obakan Yerlikaya, Ajda Çoker Gürkan, Buse Keskin, Narçin Palavan Ünsal
Purvalanol and roscovitine are specific cyclin-dependent kinase (CDK) inhibitors, which have antiproliferative and apoptotic effects on various types of cancer. Although, the apoptotic accomplishment of purvalanol and roscovitine was elucidated at the molecular level, the underlying exact of drug-induced apoptosis through mitogen-activated protein kinase (MAPK) signaling still speculative. In addition, the role of CDK inhibitors in the downregulation of extracellular signal-regulated kinase 1/2 (ERK1/2)-mediated epithelial-mesenchymal transition (EMT) remains unclear...
October 15, 2018: Journal of Cellular Biochemistry
Weiqiang Zhang, Keiqiang Liu, Yingxin Pei, Jingbo Ma, Jiang Tan, Jing Zhao
Mammalian STE20-like kinase 1 (Mst1) is well recognized as a major tumor suppressor in cancer development, growth, metabolic reprogramming, metastasis, cell death and recurrence. However, the roles of Mst1 in non-small cell lung cancer (NSCLC) A549 cell phenotypic alterations remain to be elucidated. The present study aimed to explore the functional role and underlying mechanisms of Mst1 with regards to A549 cell proliferation, migration and apoptosis; this study focused on mitochondrial homeostasis and Rho-associated coiled-coil containing protein kinase 1 (ROCK1)/F‑actin pathways...
October 8, 2018: International Journal of Oncology
Sandeep Kumar, Monisha Dhiman
Helicobacter pylori is a leading cause of gastric cancer worldwide, its type four secretary toxin CagA is cited to be primarily responsible for it. Other virulence factors such as urease, VacA, HopQ, BabA and SabA are responsible for bacterial survival in acidic environment, adherence and cellular damage but its molecular mechanism is not completely understood. A number of pathogens including bacteria, fungi and virus are involved in the regulation of cellular machinery of inflammasome. Inflammasomes are multimeric protein complexes formed after external stimuli such as PAMPs/DAMPs or salt crystals and activates cellular caspases causes inflammation via pro-inflammatory cytokines...
October 10, 2018: Microbial Pathogenesis
Rui Song, Yurong Yang, Han Lei, Guangxue Wang, Yong Huang, Wenlong Xue, Yinfang Wang, Lingling Yao, Yichun Zhu
Doxorubicin (Dox) is an efficacious antineoplastic drug but is limited used for its cardiotoxicity. Histone Deacetylase 6 (HDAC6) has been indicated to participate in cardiomyopathies, however, its role in Dox-induced cardiac injury is largely unknown. In this study, we firstly aimed to determine the role of HDAC6 in Dox-induced cardiomyopathy. Immunoblotting revealed that Dox increased HDAC6 protein level and activity and decreased α-tubulin acetylation level in vitro and vivo. HDAC6 knockout (HDAC6-/- ) mice showed obvious anti-Dox cardiotoxicity by conserved cardiac function monitored by echocardiography and the protection was reversed by Nocodazole, one drug lowering α-tubulin acetylation...
October 10, 2018: Journal of Molecular and Cellular Cardiology
Jinxia Wang, Haizhen Li, Xiaoning Wang, Tao Shen, Shuqi Wang, Dongmei Ren
Alisol B-23-acetate (AB23A), a tetracyclic triterpenoid isolated from the rhizome of Alisma orientale, has been reported to exert anti-proliferative activities in human colon, ovarian and gastric cancer cells. However, the anti-cancer effect of this compound on human lung cancer cells has not yet been thoroughly elucidated. In the present study, we investigated the effects of AB23A on the cell viability and apoptosis in human lung cancer A549 and NCI-H292 cells. The results indicated that AB23A inhibited the growth of A549 and NCI-H292 cells in dose- and time-dependent manner, however, there was only weak cytotoxicity on normal bronchial epithelial cells...
October 9, 2018: Biochemical and Biophysical Research Communications
Long-Long Xie, Feng Shi, Zheqiong Tan, Yueshuo Li, Ann M Bode, Ya Cao
Mitochondria are the major cellular energy producing organelles and intracellular source of reactive oxygen species. These organelles are responsible for driving cell life and death through mitochondrial network structure homeostasis, which is determined by a balance of fission and fusion. Recent advances revealed that a number of components of the fission and fusion machinery, including dynamin-related protein 1 (Drp1), mitofusin1/2 (Mfn1/2) and Optic atrophy 1 (OPA1) have been implicated in mitochondrial shape changes are indispensible for autophagy, apoptosis and necroptosis...
October 12, 2018: Cancer Science
Jiale Wang, Tamara Mirzapoiazova, Yi-Hung Carol Tan, Ka Ming Pang, Alex Pozhitkov, Yingyu Wang, Yang Wang, Bolot Mambetsariev, Edward Wang, Mohd W Nasser, Surinder K Batra, Dan Raz, Karen Reckamp, Prakash Kulkarni, Yanfang Zheng, Ravi Salgia
The receptor tyrosine kinase MET is frequently involved in malignant transformation and inhibiting its activity in MET-dependent cancers is associated with improved clinical outcomes. Emerging evidence also suggests that mitochondria play an essential role in tumorigenesis and Dynamin Related Protein (DRP1), a key component of the mitochondrial fission machinery, has emerged as an attractive therapeutic target. Here, we report that inhibiting MET activity with the tyrosine kinase inhibitor MGCD516 attenuates viability, migration, and invasion of non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM) cell lines in vitro, and significantly retards tumor growth in vivo...
October 12, 2018: Cancer Biology & Therapy
Ching-Wen Tsai, Jyh-Horng Wang, Tai-Horng Young
An ideal in vitro drug screening model is important for the drug development. In addition to monoculture systems, 3 dimensional (3D) coculture systems are extensively used to simulate the in vivo tumor microenvironment as cell-cell and cell-extracellular matrix interactions within the tumor tissues can be mimicked. In this study, in vitro 3D suspension coculture multicellular spheroids with core/shell cell distribution were developed on chitosan-coated surfaces. Based on the characteristic of chitosan inhibiting cell adhesion, SW620 (colon cancer cell line), 3A6 (mesenchymal stem-like cell line) and Hs68 (foreskin fibroblast line) cells could aggregate to form 3D coculture spheroids with intimate cell contacts...
October 12, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Lynae M Brayboy, Haley Clark, Laura O Knapik, Ruby E Schnirman, Gary M Wessel
Nitrogen mustard (NM) is an alkylating chemical warfare agent, and its derivatives are used in chemotherapy. Alkylating agents can cause mitochondrial damage, so exposed females may transmit damaged genomes to their children, since mitochondria are maternally inherited and oocytes are not thought to undergo mitophagy [1]. The objective of this study is to investigate NM's effects on oocyte mitochondria to understand risks facing female soldiers, cancer patients, and their children. Mice were injected intraperitoneally with NM, monitored for reproductive outcomes, and ovaries and oocytes were isolated for analysis...
October 8, 2018: Reproductive Toxicology
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