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Mitochondria Cancer

Ping Zhang, Yang Zhang, Kuikui Liu, Bin Liu, Wenping Xu, Jufang Gao, Lei Ding, Liming Tao
OBJECTIVES: The aim of study was to investigate the anticancer activities of Ivermectin (IVM) and the possible mechanisms in cells level via cell proliferation inhibition, apoptosis and migration inhibition in model cancer cell HeLa. MATERIALS AND METHODS: The MTT assay was used to study the inhibitory effect of IVM on the proliferation of Hela cells, and the cell cycle was analysed by flow cytometry. The neutral comet assay was used to study the DNA damage. The presence of apoptosis was confirmed by DAPI nuclear staining and flow cytometry...
December 4, 2018: Cell Proliferation
Reyhaneh Moradi-Marjaneh, Seyed Mahdi Hassanian, Mehraneh Mehramiz, Majid Rezayi, Gordon A Ferns, Majid Khazaei, Amir Avan
Reactive oxygen species (ROS) are produced by mitochondria during metabolism. In physiological states, the production of ROS and their elimination by antioxidants are kept in balance. However, in pathological states, elevated levels of ROS interact with susceptible cellular target compounds including lipids, proteins, and DNA and deregulate oncogenic signaling pathways that are involved in colorectal cancer (CRC) carcinogenesis. Although antioxidant compounds have been successfully used in the treatment of CRC as prevention approaches, they have also been shown in some cases to promote disease progression...
December 4, 2018: Journal of Cellular Physiology
Elena Palma, Ewald Jan Doornebal, Shilpa Chokshi
Human precision-cut liver slices represent a robust and versatile ex vivo model which retains the complex and multi-cellular histoarchitecture of the hepatic environment. As such, they represent an ideal model to investigate the mechanisms of liver injury and for the identification of novel therapeutic targets. Schematic overview to highlight the utility of precision-cut liver slices as a relevant and versatile ex-vivo model of liver disease. Top panel; Precision cut liver slices (PCLS) exposed to ethanol develop mega-mitochondria, a classical hallmark of Alcoholic Liver Disease (ALD)...
December 4, 2018: Hepatology International
Yusuke Kobayashi, Kouji Banno, Haruko Kunitomi, Takayuki Takahashi, Takashi Takeda, Kanako Nakamura, Kosuke Tsuji, Eiichiro Tominaga, Daisuke Aoki
Mammalian cells produce energy by oxidative phosphorylation under aerobic conditions. However, in the 1920s, Otto Warburg reported the so-called "Warburg effect" in which cancer cells produce ATP that is biased toward glycolysis rather than mitochondrial oxidative phosphorylation not only in anaerobic environment but also in aerobic environment. Glucose is converted into lactate without going into mitochondria after being metabolized in glycolysis. Compared with oxidative phosphorylation, the glycolysis has a faster ATP production rate but it is very inefficient, resulting in cancer cells consuming a large amount of glucose...
December 3, 2018: Journal of Obstetrics and Gynaecology Research
Saverio Marchi, Mariangela Corricelli, Alessio Branchini, Veronica Angela Maria Vitto, Sonia Missiroli, Giampaolo Morciano, Mariasole Perrone, Mattia Ferrarese, Carlotta Giorgi, Mirko Pinotti, Lorenzo Galluzzi, Guido Kroemer, Paolo Pinton
Although mitochondria play a multifunctional role in cancer progression and Ca2+ signaling is remodeled in a wide variety of tumors, the underlying mechanisms that link mitochondrial Ca2+ homeostasis with malignant tumor formation and growth remain elusive. Here, we show that phosphorylation at the N-terminal region of the mitochondrial calcium uniporter (MCU) regulatory subunit MICU1 leads to a notable increase in the basal mitochondrial Ca2+ levels. A pool of active Akt in the mitochondria is responsible for MICU1 phosphorylation, and mitochondrion-targeted Akt strongly regulates the mitochondrial Ca2+ content...
November 30, 2018: EMBO Journal
Yuxiang Zheng, Ting-Yu Lin, Gina Lee, Marcia N Paddock, Jessica Momb, Zhe Cheng, Qian Li, Dennis L Fei, Benjamin D Stein, Shivan Ramsamooj, Guoan Zhang, John Blenis, Lewis C Cantley
Mammalian folate metabolism is comprised of cytosolic and mitochondrial pathways with nearly identical core reactions, yet the functional advantages of such an organization are not well understood. Using genome-editing and biochemical approaches, we find that ablating folate metabolism in the mitochondria of mammalian cell lines results in folate degradation in the cytosol. Mechanistically, we show that QDPR, an enzyme in tetrahydrobiopterin metabolism, moonlights to repair oxidative damage to tetrahydrofolate (THF)...
November 29, 2018: Cell
Xia Du, Pengli Zhang, Hexiu Fu, Hafiz M Ahsan, Jing Gao, Qiuyun Chen
Targeting mitochondrial redox homeostasis is an appealing methodology for cancer therapeutics because of the upregulated antioxidant capacity in drug resistance cases. By coupling triphenylamine (TPA) with an excellent fluorescent group BODIPY, a novel mitochondrial-targeted fluorescent probe, BODIPY-TPA (BTPA), was synthesized and characterized. Confocal microscopic colocalization imaging indicated that BTPA exhibited a subcellular mitochondrial distribution. Cytotoxicity experiments suggested that BTPA exhibited selective anticancer activity via the induction of mitochondrial dysfunction in BGC-823 cancer cells...
November 27, 2018: International Journal of Pharmaceutics
Xiaoli Cai, Yanan Luo, Yang Song, Dong Liu, Hongye Yan, He Li, Dan Du, Chengzhou Zhu, Yuehe Lin
Despite great progress in photodynamic therapy (PDT), the therapeutic effect is still limited by some points, such as tumor hypoxia, the short lifetime and the limited action region of 1O2. Herein, a special kind of three-dimensional dendritic mesoporous silica nanosphere (3D-dendritic MSN) was synthesized and used as a robust nanocarrier to deliver abundant hydrophobic photosensitizer chlorin e6 (Ce6) to the A549 lung cancer cells. To address the tumor hypoxia issue, the nanozyme Pt nanoparticles (Pt NPs) were immobilized onto the channels of 3D-dendritic MSNs to catalyze the conversion of intracellular H2O2 to oxygen...
November 30, 2018: Nanoscale
Guohai Zhang, Liangping Li, Zhenhao Shi, Yang Yang, Yiming Wu, Huanhuan Song, Jingxian Long, Xing Lu, Shulan Zeng, Hongbin Sun, Zhen-Feng Chen, Hong Liang, Yang Peng
The real-time tracking of localization and dynamics of small molecules in organelles helps to understand their function and lock their potential targets at the subcellular resolution. To identify the mitochondria-targeting effect of small molecules (NA-17 and NA-2a) in cancer cells, we used mass spectrometry to study the distribution and enrichment of small molecules in mitochondria and the residual cytoplasm, which enables to trace action process of therapeutic molecules. Colocalization analysis with an image-guided way suggests that both NA-17 and NA-2a have mitochondria-targeting effect...
November 30, 2018: Chembiochem: a European Journal of Chemical Biology
Imran Rizvi, Shubhankar Nath, Girgis Obaid, Mustafa Kemal Ruhi, Kaitlin Moore, Shazia Bano, David Kessel, Tayyaba Hasan
A major objective in developing new treatment approaches for lethal tumors is to reduce toxicity to normal tissues while maintaining therapeutic efficacy. Photodynamic therapy (PDT) provides a mechanistically-distinct approach to treat tumors without the systemic toxicity of chemotherapy drugs. PDT involves the light-based activation of a small molecule, a photosensitizer (PS), to generate reactive molecular species (RMS) that are toxic to target tissue. Depending on the PS localization, various cellular and subcellular components can be targeted, causing selective photodamage...
November 29, 2018: Photochemistry and Photobiology
Ross A Kelly, Joseph Leedale, Andy Harrell, Daniel A Beard, Laura E Randle, Amy E Chadwick, Steven D Webb
Cancer cells depend on glucose metabolism via glycolysis as a primary energy source, despite the presence of oxygen and fully functioning mitochondria, in order to promote growth, proliferation and longevity. Glycolysis relies upon NAD+ to accept electrons in the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) reaction, linking the redox state of the cytosolic NAD+ pool to glycolytic rate. The free cytosolic NAD+/NADH ratio is involved in over 700 oxidoreductive enzymatic reactions and as such, the NAD+/NADH ratio is regarded as a metabolic readout of overall cellular redox state...
2018: PloS One
Chenming Zhao, Yuri Tolkach, Doris Schmidt, Marieta Toma, Michael H Muders, Glen Kristiansen, Stefan C Müller, Jörg Ellinger
PURPOSE: PIWI-interacting RNAs (piRNAs) have been suggested to serve as biomarkers in cancer. In this study, we validated the expression profile of two piRNAs derived from mitochondria, piR-34536 and piR-51810, in tissue and serum of a cohort of clear cell renal cell carcinoma (ccRCC) patients. METHODS: Tissue and serum samples of patients with ccRCC were collected prospectively in our biobank. Total RNA was isolated from 118 ccRCC tissues, 75 normal renal tissues as well as 30 serum samples from patients with ccRCC, and 15 serum samples from patients with non-malignant diseases...
November 28, 2018: World Journal of Urology
Sergio González Rubio, Nuria Montero Pastor, Carolina García, Víctor G Almendro-Vedia, Irene Ferrer, Paolo Natale, Luis Paz-Ares, M Pilar Lillo, Iván López-Montero
Cancer cell mitochondria represent an attractive target for oncological treatment as they have unique hallmarks that differ from their healthy counterparts, as the presence of a stronger membrane potential that can be exploited to specifically accumulate cytotoxic cationic molecules. Here, we explore the selective cytotoxic effect of 10- N -nonyl acridine orange (NAO) on human lung carcinoma H520 cells and compare them with healthy human lung primary fibroblasts. NAO is a lipophilic and positively charged molecule that promotes mitochondrial membrane adhesion that eventually leads to apoptosis when incubated at high micromolar concentration...
2018: Frontiers in Oncology
Caiyun Li, Hongyan Liu, Yunqing Yang, Xixi Xu, Tongtong Lv, Huidan Zhang, Kehang Liu, Shuangquan Zhang, Yuqing Chen
Development of antimicrobial peptides (AMPs) as highly effective and selective anticancer agents would represent great progress in cancer treatment. Here we show that myristoyl-CM4, a new synthetic analog generated by N-myristoylation of AMPs CM4, had anticancer activity against MCF-7, MDA-MB-231, MX-1 breast cancer cells (IC50 of 3-6 μM) and MDA-MB-231 xenograft tumors. The improved activity was attributed to the effect of myristoyl on the cell membrane. Flow cytometry and confocal laser scanning microscopy results showed that N-myristoylation significantly increased the membrane affinity toward breast cancer cells and also effectively mediated cellular entry...
2018: Frontiers in Pharmacology
Bowen Xie, Shuangyan Wang, Nian Jiang, Jian Jian Li
A mammalian cell houses two genomes located separately in the nucleus and mitochondria. During evolution, communications and adaptations between these two genomes occur extensively to achieve and sustain homeostasis for cellular functions and regeneration. Mitochondria provide the major cellular energy and contribute to gene regulation in the nucleus, whereas more than 98% of mitochondrial proteins are encoded by the nuclear genome. Such two-way signaling traffic presents an orchestrated dynamic between energy metabolism and consumption in cells...
November 24, 2018: Cancer Letters
Thea Heinemeyer, Monique Stemmet, Soraya Bardien, Annika Neethling
Mitochondria are critical for cellular survival, and for their proper functioning, translocation of ∼1500 proteins across the mitochondrial membranes is required. The translocase of the outer (TOMM) and inner mitochondrial membrane (TIMM) complexes are major components of this translocation machinery. Through specific processes, preproteins and other molecules are imported, translocated, and directed to specific mitochondrial compartments for their function. In this study, we review the association of subunits of these complexes with human disease...
November 27, 2018: DNA and Cell Biology
Subbarayan Sarathbabu, Satheesh Kumar Marimuthu, Souvik Ghatak, Subramanian Vidyalakshmi, Gurusubramanian Guruswami, Sankar Kumar Ghosh, Selvi Subramanian, Wenqing Zhang, Nachimuthu Senthil Kumar
OBJECTIVE: To explore the cytotoxic and apoptotic activity of the pierisin-6 protein in HPV HeLa and HepG2 cell lines. METHODS: In this study, isolation and purification of cytotoxic prierisin-6 from the larvae of Pieris napi by affinity column chromatography techniques.Characterization of full-length mRNA of pierisin-6 gene was performed using 3'/5' RACE PCR. The quantitative RT-PCR used to study the developmental stage-specific expression of pierisin-6 mRNA. The most effective concentration of pierisin-6 protein was determined by measuring cell proliferation...
November 26, 2018: Anti-cancer Agents in Medicinal Chemistry
Jingchao Xi, Meng Li, Benxin Jing, Myunggi An, Chunsong Yu, Cameron Pinnock, Yingxi Zhu, Mai Lam, Haipeng Liu
The mitochondria have emerged as a novel target for cancer chemotherapy primarily due to their central roles in energy metabolism and apoptosis regulation. Here we report a new molecular approach to achieve high levels of tumor- and mitochondria-selective delivery of the anticancer drug doxorubicin. This is achieved by molecular engineering which functionalizes doxorubicin with a hydrophobic lipid tail conju-gated by a solubility-promoting polyethylene glycol polymer (amphiphilic Doxorubicin or amph-DOX). In vivo, the amphiphile conjugated to doxorubicin exhibits a dual function: i) it binds avidly to serum albumin and hijacks albumin's circulating and transporting pathways, resulting in prolonged circulation in blood, increased accumulation in tumor, and reduced exposure to the heart; ii) it also redirects doxorubicin to mi-tochondria by altering the drug molecule's intracellular sorting and transportation routes...
November 27, 2018: ACS Applied Materials & Interfaces
Enayatollah Seydi, Mohsen Fatahi, Parvaneh Naserzadeh, Jalal Pourahmad
1. Para-phenylenediamine (PPD) is the commonest and most well-known component of hair dyes. PPD is found in more than 1000 hair dye formulations and is the most frequently used permanent hair dye component in Europe, North America, and East Asia. PPD containing hair dyes have been associated with cancer and mutagenicity. Apart from that, PPD has potential toxicity which includes acute toxicity such as allergic contact dermatitis and subacute toxicity. 2. In this study, we examined the effects of the PPD composition on the skin-isolated fibroblast cells...
November 25, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Bing Han, Pu Jiang, Heshan Xu, Wuyang Liu, Jian Zhang, Siqi Wu, Liangyu Liu, Wenyu Ma, Xuegang Li, Xiaoli Ye
Lung cancer is the worldwide leading cause of cancer-related death. Here, we described the synthesis and the anticancer activity of a novel coptisine derivative 8-cetylcoptisine (CCOP) on lung carcinoma in vitro and in vivo. CCOP inhibited the cell viability of A549, BGC-823, MDA-MB-231, HCT-116 and HepG2 cell lines. In A549 cells, CCOP induced apoptosis, G0/G1 cell cycle arrest and decreased mitochondrial membrane potential (MMP) in a dose-dependent manner. Western blot analysis showed that CCOP increased the expression of Bcl-2-associated X protein (Bax), cleaved caspase 3 and 9, while decreased B-cell lymphoma 2 (Bcl-2), cyclins D and E, cyclin dependent kinases (CDKs) 2, 4 and 6, along with the inactivation of the upstream phosphoinositide 3-kinase (Pi3k)/protein kinase B (Akt) signaling...
November 22, 2018: Chemico-biological Interactions
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