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https://www.readbyqxmd.com/read/29352318/temozolomide-induced-increase-of-tumorigenicity-can-be-diminished-by-targeting-of-mitochondria-in-in-vitro-models-of-patient-individual-glioblastoma
#1
Doreen William, Madlin Walther, Björn Schneider, Michael Linnebacher, Carl Friedrich Classen
Glioblastoma multiforme (GBM) is a highly heterogeneous and aggressive brain tumor with a dismal prognosis. Development of resistance towards cytostatic drugs like the GBM standard drug temozolomide is a severe problem in GBM treatment. One potential source of GBM relapse could be so called cancer stem like cells (CSCs). These represent an undifferentiated subpopulation of cells with high potential for tumor initiation. Furthermore, it has been shown that differentiated GBM cells can regain CSC properties when exposed to continuous temozolomide treatment in vitro...
2018: PloS One
https://www.readbyqxmd.com/read/29351723/mitochondrial-uncoupling-proteins-subtle-regulators-of-cellular-redox-signaling
#2
Petr Jezek, Blanka Holendová, Keith D Garlid, Martin Jaburek
SIGNIFICANCE: Mitochondria are the energetic, metabolic, redox and information signaling centers of the cell. Substrate pressure, mitochondrial network dynamics and cristae morphology state are integrated by the protonmotive force Δp or its potential component, ΔΨ, which are attenuated by proton backflux into the matrix, termed uncoupling. The mitochondrial uncoupling proteins (UCP1-5) play an eminent role in the regulation of each of the above aspects, being involved in numerous physiological events including redox signaling...
January 19, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29349780/protective-effect-of-bled-exposed-conditioned-media-on-cell-injury
#3
Phil-Sun Oh, Eun-Mi Kim, Minjoo Kim, In Sun Kim, Yeon-Hee Han, SeokTae Lim, Myung-Hee Sohn, Myoung-Hwan Ko, Hwan-Jeong Jeong
Previous studies have reported that 450 nm blue light emitting diode (BLED) induces apoptosis through a mitochondria-mediated pathway in cancer cells and reduces the early stage tumor growth. The present study was performed to determine the effects of BLED-irradiated cell metabolites on cell injury. Our results showed that conditioned medium (CM) from cells irradiated with low-dose BLED (LCM) inhibited apoptosis and increased cell survival. Cell protection-related proteins were identified in cell metabolites of CM and LCM using 2-DE and MALDI-TOF analysis...
January 19, 2018: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/29349707/piperazine-clubbed-with-2-azetidinone-derivatives-suppresses-proliferation-migration-and-induces-apoptosis-in-human-cervical-cancer-hela-cells-through-oxidative-stress-mediated-intrinsic-mitochondrial-pathway
#4
Rashmin Khanam, Raj Kumar, Iram Iqbal Hejazi, Syed Shahabuddin, Ramovatar Meena, Vikrant Jayant, Prabhat Kumar, Abdul Roouf Bhat, Fareeda Athar
Piperazine scaffolds or 2-azetidinone pharmacophores have been reported to show anti-cancer activities and apoptosis induction in different types of cancer cells. However, the mechanistic studies involve in induction of apoptosis addressing these two moieties for human cervical cancer cells remain uncertain. The present study emphasizes on the anti-proliferating properties and mechanism involved in induction of apoptosis for these structurally related azoles derivatives in HeLa cancer cells. 1-Phenylpiperazine clubbed with 2-azetidione derivatives (5a-5h) were synthesized, characterized using various spectroscopic techniques and evaluated for their in-vitro anti-proliferative activities and induction of apoptosis...
January 18, 2018: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29348461/loss-of-cdk5-in-breast-cancer-cells-promotes-ros-mediated-cell-death-through-dysregulation-of-the-mitochondrial-permeability-transition-pore
#5
Saranya NavaneethaKrishnan, Jesusa L Rosales, Ki-Young Lee
Cdk5, which plays a role in the development and progression of many human cancers, localizes in the mitochondria, a key determinant of apoptotic cell death. Cdk5 is upregulated in breast cancer cells but it was shown that Cdk5 loss increases chemotherapy-induced apoptosis. However, the molecular mechanism by which Cdk5 loss promotes cell death remains unclear. Here, we investigate the possibility that Cdk5 loss activates the intrinsic apoptotic pathway in breast cancer cells. We demonstrate that Cdk5-deficient breast cancer cells exhibit increased mitochondrial depolarization, mitochondrial ROS levels, and mitochondrial fragmentation that is associated with an increase in both intracellular Ca2+ level and calcineurin activity, and DRP1 S637 dephosphorylation...
January 19, 2018: Oncogene
https://www.readbyqxmd.com/read/29348439/dual-suppression-of-inner-and-outer-mitochondrial-membrane-functions-augments-apoptotic-responses-to-oncogenic-mapk-inhibition
#6
Madhavika N Serasinghe, Jesse D Gelles, Kent Li, Lauren Zhao, Franco Abbate, Marie Syku, Jarvier N Mohammed, Brateil Badal, Cuahutlehuanitzin A Rangel, Kyle L Hoehn, Julide Tok Celebi, Jerry Edward Chipuk
Mitogen-activated protein kinase (MAPK) pathway inhibitors show promise in treating melanoma, but are unsuccessful in achieving long-term remission. Concordant with clinical data, BRAFV600E melanoma cells eliminate glycolysis upon inhibition of BRAFV600E or MEK with the targeted therapies Vemurafenib or Trametinib, respectively. Consequently, exposure to these therapies reprograms cellular metabolism to increase mitochondrial respiration and restrain cell death commitment. As the inner mitochondrial membrane (IMM) is sub-organellar site of oxidative phosphorylation (OXPHOS), and the outer mitochondrial membrane (OMM) is the major site of anti-apoptotic BCL-2 protein function, we hypothesized that suppressing these critical mitochondrial membrane functions would be a rational approach to maximize the pro-apoptotic effect of MAPK inhibition...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348263/phosphoinositide-3-kinase-gamma-inhibition-protects-from-anthracycline-cardiotoxicity-and-reduces-tumor-growth
#7
Mingchuan Li, Valentina Sala, Maria Chiara De Santis, James Cimino, Paola Cappello, Nicola Pianca, Anna Di Bona, Jean Piero Margaria, Miriam Martini, Edoardo Lazzarini, Flora Pirozzi, Luca Rossi, Irene Franco, Julia Bornbaum, Jacqueline Heger, Susanne Rohrbach, Alessia Perino, Carlo G Tocchetti, Braulio H F Lima, Mauro M Teixeira, Paolo E Porporato, Rainer Schulz, Annalisa Angelini, Marco Sandri, Pietro Ameri, Sebastiano Sciarretta, Roberto César P Lima-Júnior, Marco Mongillo, Tania Zaglia, Fulvio Morello, Francesco Novelli, Emilio Hirsch, Alessandra Ghigo
Background -Anthracyclines, such as doxorubicin (DOX), are potent anti-cancer agents for the treatment of solid tumors and hematological malignancies. However, their clinical use is hampered by cardiotoxicity. This study sought to investigate the role of PI3Kγ in DOX-induced cardiotoxicity and the potential cardio-protective and anti-cancer effects of PI3Kγ inhibition. Methods -Mice expressing a kinase-inactive PI3Kγ or receiving PI3Kγ selective inhibitors were subjected to chronic DOX treatment. Cardiac function was analyzed by echocardiography and DOX-mediated signaling was assessed in whole hearts or in isolated cardiomyocytes...
January 18, 2018: Circulation
https://www.readbyqxmd.com/read/29346731/direct-polymerization-of-the-arsenic-drug-penao-to-obtain-nanoparticles-with-high-thiol-reactivity-and-anti-cancer-efficiency
#8
Janina-Miriam Noy, Hongxu Lu, Philip Hogg, Jia-Lin Yang, Martina H Stenzel
PENAO (4-(N-(S-penicillaminylacetyl)amino) phenylarsonous acid), which is a mitochondria inhibitor that reacts with adenine nucleotide translocator (ANT), is currently being trialed in patients with solid tumors. To increase the stability of the drug, the formation of nanoparticles has been proposed. Herein, the direct synthesis of polymeric micelles based on the anti-cancer drug PENAO is presented. PENAO is readily available for amidation reaction to form PENAO MA (4-(N-(S-penicillaminylacetyl) amino) phenylarsonous acid methacrylamide) which undergoes RAFT (reversible addition fragmentation chin transfer) polymerization with poly(polyethylene glycol methyl ether methacrylate) (PEGMA) as comonomer and poly(methylmethacrylate) (pMMA) as chain transfer agent, resulting in p(MMA)-b-p(PEG-co-PENAO) block copolymers with 3-15 wt...
January 18, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29345195/mitochondrial-dysfunction-and-pulmonary-hypertension-cause-effect-or-both
#9
Jeffrey D Marshall, Isabel Bazan, Yi Zhang, Wassim H Fares, Patty J Lee
Pulmonary hypertension describes a heterogeneous disease defined by increased pulmonary artery pressures, and progressive increase in pulmonary vascular resistance due to pathologic remodeling of the pulmonary vasculature involving pulmonary endothelial cells, pericytes, and smooth muscle cells.  This process occurs under various conditions, and though these populations vary, the clinical manifestations are the same: progressive dyspnea, increases in right ventricular (RV) afterload and dysfunction, RV-pulmonary artery uncoupling, and right-sided heart failure with systemic circulatory collapse...
January 18, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29344554/pulling-the-plug-halting-cancer-s-theft-of-mitochondria
#10
EDITORIAL
Christopher R Marlein, Lyubov Zaitseva, Stuart A Rushworth
No abstract text is available yet for this article.
November 2017: Oncoscience
https://www.readbyqxmd.com/read/29343628/keeping-the-home-fires-burning-amp-activated-protein-kinase
#11
REVIEW
D Grahame Hardie
Living cells obtain energy either by oxidizing reduced compounds of organic or mineral origin or by absorbing light. Whichever energy source is used, some of the energy released is conserved by converting adenosine diphosphate (ADP) to adenosine triphosphate (ATP), which are analogous to the chemicals in a rechargeable battery. The energy released by the conversion of ATP back to ADP is used to drive most energy-requiring processes, including cell growth, cell division, communication and movement. It is clearly essential to life that the production and consumption of ATP are always maintained in balance, and the AMP-activated protein kinase (AMPK) is one of the key cellular regulatory systems that ensures this...
January 2018: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/29343514/trpm2-channel-mediated-regulation-of-autophagy-maintains-mitochondrial-function-and-promotes-gastric-cancer-cell-survival-via-the-jnk-signaling-pathway
#12
Shekoufeh Almasi, Barry E Kennedy, Mariam El Aghil, Andra M Sterea, Shashi Gujar, Santiago Partida-Sánchez, Yassine El Hiani
A lack of effective treatment is one of the main factors contributing to gastric cancer-related death. Discovering effective targets and understanding their underlying anticancer mechanism is key to achieving the best response to treatment and to limiting side effects. Although recent studies have shown that the cation channel transient receptor potential melastatin-2 (TRPM2) is crucial for cancer cell survival, the exact mechanism remains unclear, limiting its therapeutic potential. Here, using molecular and functional assays, we investigated the role of TRPM2 in survival of gastric cancer cells...
January 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29342359/semiconducting-photothermal-nanoagonist-for-remote-controlled-specific-cancer-therapy
#13
Xu Zhen, Chen Xie, Yuyan Jiang, Xiangzhao Ai, Bengang Xing, Kanyi Pu
Nanomedicines have shown success in cancer therapy, but the pharmacological actions of most nanomedicine are often nonspecific to cancer cells because of utilization of the therapeutic agents that induce cell apoptosis from inner organelles. We herein report the development of semiconducting photothermal nanoagonists that can remotely and specifically initiate the apoptosis of cancer cells from cell membrane. The organic nanoagonists comprise semiconducting polymer nanoparticles (SPNs) and capsaicin (Cap) as the photothermally-responsive nanocarrier and the agonist for activation of transient receptor potential cation channel subfamily V member 1 (TRPV1), respectively...
January 17, 2018: Nano Letters
https://www.readbyqxmd.com/read/29341317/apoptosis-induction-in-k562-human-myelogenous-leukaemia-cells-is-connected-to-the-modulation-of-wnt-%C3%AE-catenin-signalling-by-bhx-a-novel-pyrazoline-derivative
#14
Hanmei Bao, Qing Zhang, Yibo Du, Cai Zhang, Hui Xu, Zhongling Zhu, Zhao Yan
OBJECTIVES: The goal of this study was to explore the effects of BHX on human chronic myeloid leukaemia (CML) cells and to elucidate the underlying molecular mechanism. MATERIALS AND METHODS: CML cell line K562 cells were treated with BHX. The effects of BHX on cell proliferation, apoptosis and cell cycle were detected. Subsequently, the caspase, ATP activity, Ca2+ , ROS and mitochondrial membrane potential (MMP) levels treated with various concentrations of BHX were analysed...
January 16, 2018: Cell Proliferation
https://www.readbyqxmd.com/read/29340082/reciprocal-sensitivity-of-diffuse-large-b-cell-lymphoma-cells-to-bcl-2-inhibitors-bird-2-versus-venetoclax
#15
Tamara Vervloessem, Haidar Akl, Thomas Tousseyn, Humbert De Smedt, Jan B Parys, Geert Bultynck
Bcl-2 is often upregulated in cancers to neutralize the BH3-only protein Bim at the mitochondria. BH3 mimetics (e.g. ABT-199 (venetoclax)) kill cancer cells by targeting Bcl-2's hydrophobic cleft and disrupting Bcl-2/Bim complexes. Some cancers with elevated Bcl-2 display poor responses towards BH3 mimetics, suggesting an additional function for anti-apoptotic Bcl-2 in these cancers. Indeed, Bcl-2 via its BH4 domain prevents cytotoxic Ca2+ release from the endoplasmic reticulum (ER) by directly inhibiting the inositol 1,4,5-trisphosphate receptor (IP3R)...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340076/mitochondrial-ros-activates-erk-autophagy-pathway-as-a-protected-mechanism-against-deoxypodophyllotoxin-induced-apoptosis
#16
Sang-Hun Kim, Kwang-Youn Kim, Sul-Gi Park, Sun-Nyoung Yu, Young-Wook Kim, Hyo-Won Nam, Hyun-Hee An, Young-Woo Kim, Soon-Cheol Ahn
Deoxypodophyllotoxin (DPT) is a naturally occurring flavolignan isolated from Anthriscus sylvestris. Recently, it has been reported that DPT inhibits tubulin polymerization and induces G2/M cell cycle arrest followed by apoptosis through multiple cellular processes. Despite these findings, details regarding the cellular and molecular mechanisms underlying the DPT-mediated cell death have been poorly understood. To define a mechanism of DPT-mediated cell death response, we examined whether DPT activates signaling pathways for autophagy and apoptosis...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340048/alteration-of-mitochondrial-biogenesis-promotes-disease-progression-in-multiple-myeloma
#17
Xin Zhan, Wenjie Yu, Reinaldo Franqui-Machin, Melissa L Bates, Kalyan Nadiminti, Huojun Cao, Brad A Amendt, Yogesh Jethava, Ivana Frech, Fenghuang Zhan, Guido Tricot
Many cancers, including multiple myeloma (MM), retain more cytosolic iron to promote tumor cell growth and drug resistance. Higher cytosolic iron promotes oxidative damage due to its interaction with reactive oxygen species generated by mitochondria. The variation of mitochondrial biogenesis in different stages of MM disease was evaluated using gene expression profiles in a large clinical dataset. Sixteen of 18mitochondrial biogenesis related gene sets, including mitochondrial biogenesis signature and oxidative phosphorylation, were increased in myeloma cells compared with normal plasma cells and high expression was associated with an inferior patient outcome...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29338573/triphenylphosphine-docetaxel-conjugate-incorporated-albumin-nanoparticles-for-cancer-treatment
#18
Gantumur Battogtokh, Oyuntuya Gotov, Jee He Kang, Jinsung Cho, Tae Ho Jeong, Ganzorig Chimed, Young Tag Ko
AIM: The objective of this study was to develop a mitochondria-targeted anticancer drug, docetaxel (DTX), for chemotherapy. MATERIALS & METHODS: The DTX was conjugated to 4-carboxybutyl triphenylphosphonium (TPP) to enhance mitochondrial targeting, and the TPP-DTX conjugate was further loaded into folate-cholesteryl albumin (FA-chol-BSA) nanoparticles (NPs) to improve its biocompatibility. RESULTS & CONCLUSION: In vitro studies showed that TPP-DTX and its NP primarily accumulated in the mitochondria; generated high reactive oxygen species, leading to mitochondrial disruption and cell apoptosis; and had a higher cytotoxicity against cancer cells...
January 17, 2018: Nanomedicine
https://www.readbyqxmd.com/read/29338036/static-magnetic-field-enhances-the-anticancer-efficacy-of-capsaicin-on-hepg2-cells-via-capsaicin-receptor-trpv1
#19
Wei-Ting Chen, Guan-Bo Lin, Shu-Hui Lin, Chueh-Hsuan Lu, Chih-Hsiung Hsieh, Bo-Lun Ma, Chih-Yu Chao
Static magnetic field (SMF) has shown some possibilities for cancer therapies. In particular, the combinational effect between SMF and anti-cancer drugs has drawn scientists' attentions in recent years. However, the underlying mechanism for the drug-specific synergistic effect is far from being understood. Besides, the drugs used are all conventional chemotherapy drugs, which may cause unpleasant side effects. In this study, our results demonstrate for the first time that SMF could enhance the anti-cancer effect of natural compound, capsaicin, on HepG2 cancer cells through the mitochondria-dependent apoptosis pathway...
2018: PloS One
https://www.readbyqxmd.com/read/29337889/reactive-oxygen-species-and-mitochondrial-dynamics-the-yin-and-yang-of-mitochondrial-dysfunction-and-cancer-progression
#20
REVIEW
Jan Ježek, Katrina F Cooper, Randy Strich
Mitochondria are organelles with a highly dynamic ultrastructure maintained by a delicate equilibrium between its fission and fusion rates. Understanding the factors influencing this balance is important as perturbations to mitochondrial dynamics can result in pathological states. As a terminal site of nutrient oxidation for the cell, mitochondrial powerhouses harness energy in the form of ATP in a process driven by the electron transport chain. Contemporaneously, electrons translocated within the electron transport chain undergo spontaneous side reactions with oxygen, giving rise to superoxide and a variety of other downstream reactive oxygen species (ROS)...
January 16, 2018: Antioxidants (Basel, Switzerland)
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