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https://www.readbyqxmd.com/read/28548464/control-of-cell-death-and-mitochondrial-fission-by-erk1-2-map-kinase-signalling
#1
REVIEW
Simon J Cook, Kate Stuart, Rebecca Gilley, Matthew J Sale
The ERK1/2 signalling pathway is best known for its role in connecting activated growth factor receptors to changes in gene expression due to activated ERK1/2 entering the nucleus and phosphorylating transcription factors. However, active ERK1/2 also translocate to a variety of other organelles including the endoplasmic reticulum, endosomes, golgi and mitochondria to access specific substrates and influence cell physiology. In this article we review two aspects of ERK1/2 signalling at the mitochondria that are involved in regulating cell fate decisions...
May 26, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28544069/cd38-enhances-the-proliferation-and-inhibits-the-apoptosis-of-cervical-cancer-cells-by-affecting-the-mitochondria-functions
#2
Shan Liao, Songshu Xiao, Hongxiang Chen, Manying Zhang, Zhifang Chen, Yuehua Long, Lu Gao, Guangchao Zhu, Junyu He, Shuping Peng, Wei Xiong, Zhaoyang Zeng, Zheng Li, Ming Zhou, Xiaoling Li, Jian Ma, Minghua Wu, Juanjuan Xiang, Guiyuan Li, Yanhong Zhou
Cervical cancer is one of the most common malignant tumors in women all over the world. The exact mechanism of occurrence and development of cervical cancer has not been fully elucidated. CD38 is a type II transmembrane glycoprotein, which was found to mediate diverse activities, including signal transduction, cell adhesion, and cyclic ADP-ribose synthesis. Here, we reported that CD38 promoted cell proliferation and inhibited cell apoptosis in cervical cancer cells by affecting the mitochondria functions. We established stable cervical cancer cell lines with CD38 over-expressed...
May 23, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28543935/neurodegeneration-in-ataxia-telangiectasia-multiple-roles-of-atm-kinase-in-cellular-homeostasis
#3
REVIEW
Kay Rui Choy, Dianne J Watters
Ataxia-Telangiectasia (A-T) is characterized by neuronal degeneration, cancer, diabetes, immune deficiency and increased sensitivity to ionizing radiation. A-T is attributed to the deficiency of the protein kinase coded by the ATM (Ataxia-Telangiectasia Mutated) gene. ATM is a sensor of DNA Double Strand Breaks and signals to cell cycle checkpoints and the DNA repair machinery. ATM phosphorylates numerous substrates and activates many cell-signalling pathways. There has been considerable debate about whether a defective DNA damage response is causative of the neurological aspects of the disease...
May 22, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28539531/synergistic-activity-of-an-antimetabolite-drug-and-tyrosine-kinase-inhibitors-against-breast-cancer-cells
#4
Yushan Wu, Dongxing Zhang, Baofan Wu, Yuan Quan, Dongwu Liu, Yanyan Li, Xiuzhen Zhang
Antimetabolite drugs, including the adenosine deaminase inhibitor cladribine, have been shown to induce apoptosis in a variety of cancer cells, and have been widely used in clinical trials of various cancers in conjunction with tyrosine kinase inhibitors (TKIs). Combination treatment with cladribine and gefitinib or dasatinib is expected to have a synergistic inhibitory effect on breast cancer cell growth. Our results demonstrated that the combination treatment had synergistic activity against MCF-7 cells, enhanced G2/M cell arrest and ROS generation, and increased the loss of mitochondrial membrane potential and cell apoptosis...
May 25, 2017: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28538732/cps1-maintains-pyrimidine-pools-and-dna-synthesis-in-kras-lkb1-mutant-lung-cancer-cells
#5
Jiyeon Kim, Zeping Hu, Ling Cai, Kailong Li, Eunhee Choi, Brandon Faubert, Divya Bezwada, Jaime Rodriguez-Canales, Pamela Villalobos, Yu-Fen Lin, Min Ni, Kenneth E Huffman, Luc Girard, Lauren A Byers, Keziban Unsal-Kacmaz, Christopher G Peña, John V Heymach, Els Wauters, Johan Vansteenkiste, Diego H Castrillon, Benjamin P C Chen, Ignacio Wistuba, Diether Lambrechts, Jian Xu, John D Minna, Ralph J DeBerardinis
Metabolic reprogramming by oncogenic signals promotes cancer initiation and progression. The oncogene KRAS and tumour suppressor STK11, which encodes the kinase LKB1, regulate metabolism and are frequently mutated in non-small-cell lung cancer (NSCLC). Concurrent occurrence of oncogenic KRAS and loss of LKB1 (KL) in cells specifies aggressive oncological behaviour. Here we show that human KL cells and tumours share metabolomic signatures of perturbed nitrogen handling. KL cells express the urea cycle enzyme carbamoyl phosphate synthetase-1 (CPS1), which produces carbamoyl phosphate in the mitochondria from ammonia and bicarbonate, initiating nitrogen disposal...
May 24, 2017: Nature
https://www.readbyqxmd.com/read/28537893/alpha-mangostin-induces-apoptosis-through-activation-of-reactive-oxygen-species-and-ask1-p38-signaling-pathway-in-cervical-cancer-cells
#6
Chien-Hsing Lee, Tsung-Ho Ying, Hui-Ling Chiou, Shu-Ching Hsieh, Shiua-Hua Wen, Ruey-Hwang Chou, Yi-Hsien Hsieh
Alpha-mangostin, a natural xanthonoid, has been reported to possess the anti-cancer property in various types of human cancer. However, its effects and mechanism of α-mangostin in cervical cancer remain unclear. We found that α-mangostin effectively inhibited cell viability, resulted in loss of mitochondrial membrane potential (MMP), release of cytochrome C, increase of Bax, decrease of Bcl-2, and activation of caspase-9/caspase-3 cascade in cervical cancer cells. Alpha-mangostin elevated the contents of reactive oxygen species (ROS) to activate p38...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28534964/tamoxifen-promotes-apoptosis-and-inhibits-invasion-in-estrogen%C3%A2-positive-breast-cancer-mcf%C3%A2-7-cells
#7
Wei Li, Xingpeng Shi, Yan Xu, Jianmei Wan, Shaohua Wei, Ran Zhu
Tamoxifen (TAM) is the earliest non-steroidal antiestrogen drug, which has been widely used in endocrine therapy targeting breast cancer. The aim of the present study was to investigate the effect of TAM on the proliferation, apoptosis, migration and invasion of the estrogen‑positive (ER+) breast cancer cell line MCF‑7 in vitro, and elucidate its mechanisms. It was demonstrated that TAM suppressed proliferation, migration and invasion, and induced apoptosis in MCF‑7 cells. Further investigation revealed that the mitochondrial membrane potential and the amount of ATP were significantly decreased following the treatment of MCF‑7 cells with TAM...
May 18, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28534823/preparation-and-in-vitro-photodynamic-activity-of-glucosylated-zinc-ii-phthalocyanines-as-underlying-targeting-photosensitizers
#8
Jian-Yong Liu, Chen Wang, Chun-Hui Zhu, Zhi-Hong Zhang, Jin-Ping Xue
Two novel glucosylated zinc(ІІ) phthalocyanines 7a-7b, as well as the acetyl-protected counterparts 6a-6b, have been synthesized by the Cu(I)-catalyzed 1,3-dipolar cycloaddition between the propargylated phthalocyanine and azide-substituted glucoses. All of these phthalocyanines were characterized with various spectroscopic methods and studied for their photo-physical, photo-chemical, and photo-biological properties. With glucose as the targeting unit, phthalocyanines 7a-7b exhibit a specific affinity to MCF-7 breast cancer cells over human embryonic lung fibroblast (HELF) cells, showing higher cellular uptake...
May 19, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28534323/-era-of-enhanced-recovery-after-surgery-and-robotic-gastric-cancer-surgery
#9
Yanbing Zhou
Enhanced recovery after surgery (ERAS) has been rapidly developing by combining several techniques with evidence-based adjustments, including preoperative education, preoperative carbohydrate loading, epidural or regional anesthesia, early initiation of enteral nutrition, ambulation and multi-modal pain management. The core part of ERAS is to reduce and reverse surgical stress and therefore greatly improve clinical outcome. Under the guidance of ERAS, perioperative management of robotic gastric cancer operation should follow the basic principles of ERAS and clinical pathway to maximize the advantages of the robotic surgery...
May 25, 2017: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/28531122/microwave-assisted-synthesis-of-imidazo-4-5-f-1-10-phenanthroline-derivatives-as-apoptosis-inducers-in-chemotherapy-by-stabilizing-bcl-2-g-quadruplex-dna
#10
Li Li, Jie-Qiong Cao, Hui-Min Liu, Qiong Wu, Qiu-Hui Pan, Zhi-Ping Zeng, Yu-Tao Lan, Yu-Mei Li, Wen-Jie Mei, Xi-Cheng Wang, Wen-Jie Zheng
Herein, a series of imidazo[4,5-f][1,10] phenanthroline derivatives RPIP (PIP = imidazo [4,5-f][1,10] phenanthroline, R = NO₂, 1; CF₃, 2; Cl, 3; OH, 4) have been synthesized in yields of 82.3-94.7% at 100 °C under the irradiation of microwave. MTT assay has been utilized to evaluate the inhibitory activity (IC50) of these compounds against the growth of various tumor cells, and the results revealed that these compounds, especially 1, exhibited excellent inhibitory activity against the growth of A549 cells with IC50 of 15...
May 20, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28529950/tumor-selective-cytotoxicity-of-nitidine-results-from-its-rapid-accumulation-into-mitochondria
#11
Hironori Iwasaki, Masashi Inafuku, Naoyuki Taira, Seikoh Saito, Hirosuke Oku
We identified a nitidine- (NTD-) accumulating organelle and evaluated the net cytotoxicity of accumulated NTD. To evaluate tumor cell selectivity of the drug, we evaluated its selective cytotoxicity against 39 human cancer cell lines (JFCR39 panel), and the profile was compared with those of known anticancer drugs. Organelle specificity of NTD was visualized using organelle-targeted fluorescent proteins. Real-time analysis of cell growth, proliferation, and cytotoxicity was performed using the xCELLigence system...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28529636/a-new-green-titania-with-enhanced-nir-absorption-for-mitochondria-targeted-cancer-therapy
#12
Juan Mou, Tianquan Lin, Fuqiang Huang, Jianlin Shi, Hangrong Chen
A new kind of green titania (G-TiO2-x ) with obvious green color was facilely synthesized from black titania (B-TiO2-x ) through subsequently strong ultrasonication. Comparatively, this stable G-TiO2-x shows much enhanced near infrared (NIR) absorption, especially around 920 nm, which can be ascribed to the obvious change of TiO2-x lattice order owing to the effect of ultrasonication. This feature enables G-TiO2-x to be stimulated with 980 nm laser in the combined photodynamic therapy (PDT) and photothermal therapy (PTT), which is greatly beneficial for improving tissue penetration depth...
2017: Theranostics
https://www.readbyqxmd.com/read/28529179/mitochondria-and-endoplasmic-reticulum-targets-for-a-better-insulin-sensitivity-in-skeletal-muscle
#13
REVIEW
Alexis Boulinguiez, Bart Staels, Helene Duez, Steve Lancel
Obesity and its associated metabolic disorders represent a major health burden, with economic and social consequences. Although adapted lifestyle and bariatric surgery are effective in reducing body weight, obesity prevalence is still rising. Obese individuals often become insulin-resistant. Obesity impacts on insulin responsive organs, such as the liver, adipose tissue and skeletal muscle, and increases the risk of cardiovascular diseases, type 2 diabetes and cancer. In this review, we discuss the effects of obesity and insulin resistance on skeletal muscle, an important organ for the control of postprandial glucose...
May 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28526133/metabolic-reprogramming-and-oncogenesis-one-hallmark-many-organelles
#14
A S H Costa, C Frezza
The process of tumorigenesis can be described by a series of molecular features, among which alteration of cellular metabolism has recently emerged. This metabolic rewiring fulfills the energy and biosynthetic demands of fast proliferating cancer cells and amplifies their metabolic repertoire to survive and proliferate in the poorly oxygenated and nutrient-deprived tumor microenvironment. During the last decade, the complex reprogramming of cancer cell metabolism has been widely investigated, revealing cancer-specific metabolic alterations...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28523104/3-aroyl-1-4-diarylpyrroles-inhibit-chronic-myeloid-leukemia-cell-growth-through-an-interaction-with-tubulin
#15
Giuseppe La Regina, Ruoli Bai, Antonio Coluccia, Valeria Famiglini, Sara Passacantilli, Valentina Naccarato, Giorgio Ortar, Carmela Mazzoccoli, Vitalba Ruggieri, Francesca Agriesti, Claudia Piccoli, Tiziana Tataranni, Marianna Nalli, Andrea Brancale, Stefania Vultaggio, Ciro Mercurio, Mario Varasi, Concetta Saponaro, Sara Sergio, Michele Maffia, Addolorata Maria Luce Coluccia, Ernest Hamel, Romano Silvestri
We designed 3-aroyl-1,4-diarylpyrrole (ARDAP) derivatives as potential anticancer agents having different substituents at the 1- or 4-phenyl ring. ARDAP compounds exhibited potent inhibition of tubulin polymerization, binding of colchicine to tubulin, and cancer cell growth. ARDAP derivative 10 inhibited the proliferation of BCR/ABL-expressing KU812 and LAMA84 cells from chronic myeloid leukemia (CML) patients in blast crisis and of hematopoietic cells ectopically expressing the imatinib mesylate (IM)-sensitive KBM5-WT or its IM-resistant KBM5-T315I mutation...
May 11, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28521307/downregulation-of-x-linked-inhibitor-of-apoptosis-protein-by-7-benzylidenenaltrexone-maleate-sensitizes-pancreatic-cancer-cells-to-trail-induced-apoptosis
#16
So Young Kim, Sojung Park, SeonA Yoo, Jin Kyung Rho, Eun Sung Jun, Suhwan Chang, Kyung Kon Kim, Song Cheol Kim, Inki Kim
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential biological anticancer agent. However, a wide range of human primary cancers, including pancreatic cancer, display resistance to apoptosis induction by TRAIL. Therefore, this resistance needs to be overcome to allow TRAIL to be successfully used in cancer therapy. In this study, we performed a compound screen to isolate TRAIL sensitizers and found that one of the identified compounds, 7-benzylidenenaltrexone maleate (BNTX), sensitized pancreatic cancer cells to TRAIL-induced apoptotic cell death...
May 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28521246/synthesis-of-novel-dibenzoxanthene-derivatives-and-observation-of-apoptosis-in-human-hepatocellular-cancer-cells
#17
Hui-Hui Yang, Yun-Jun Liu, Xiu-Zhen Wang
We have synthesized dibenzoxanthene derivatives 2a-2i via nucleophilic substitution of methoxyl group and evaluated underlying antitumor molecular mechanism of target compounds. Compounds showed high cytotoxic activities against BEL-7402, A549, HeLa and MG-63 cancer cells in the µM range. These compounds inhibited the cell growth of BEL-7402 cells at S or G2/M phase. The compounds 2a-2i also induced the apoptosis of BEL-7402 cells. In addition, compounds enhanced the level of intramolecular ROS and decreased the mitochondrial membrane potential...
May 4, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28516063/modulation-of-ca-2-signaling-by-anti-apoptotic-b-cell-lymphoma-2-proteins-at-the-endoplasmic-reticulum-mitochondrial-interface
#18
REVIEW
Tim Vervliet, Eva Clerix, Bruno Seitaj, Hristina Ivanova, Giovanni Monaco, Geert Bultynck
Mitochondria are important regulators of cell death and cell survival. Mitochondrial Ca(2+) levels are critically involved in both of these processes. On the one hand, excessive mitochondrial Ca(2+) leads to Ca(2+)-induced mitochondrial outer membrane permeabilization and thus apoptosis. On the other hand, mitochondria need Ca(2+) in order to efficiently fuel the tricarboxylic acid cycle and maintain adequate mitochondrial bioenergetics. For obtaining this Ca(2+), the mitochondria are largely dependent on close contact sites with the endoplasmic reticulum (ER), the so-called mitochondria-associated ER membranes...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28516062/endoplasmic-reticulum-mitochondrial-ca-2-fluxes-underlying-cancer-cell-survival
#19
REVIEW
Hristina Ivanova, Martijn Kerkhofs, Rita M La Rovere, Geert Bultynck
Calcium ions (Ca(2+)) are crucial, ubiquitous, intracellular second messengers required for functional mitochondrial metabolism during uncontrolled proliferation of cancer cells. The mitochondria and the endoplasmic reticulum (ER) are connected via "mitochondria-associated ER membranes" (MAMs) where ER-mitochondria Ca(2+) transfer occurs, impacting the mitochondrial biology related to several aspects of cellular survival, autophagy, metabolism, cell death sensitivity, and metastasis, all cancer hallmarks. Cancer cells appear addicted to these constitutive ER-mitochondrial Ca(2+) fluxes for their survival, since they drive the tricarboxylic acid cycle and the production of mitochondrial substrates needed for nucleoside synthesis and proper cell cycle progression...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28515021/sulforaphene-an-isothiocyanate-present-in-radish-plants-inhibits-proliferation-of-human-breast-cancer-cells
#20
Anna Pawlik, Marta Wała, Aleksandra Hać, Agnieszka Felczykowska, Anna Herman-Antosiewicz
BACKGROUND: Isothiocyanates derived from the Brassicaceae plants possess chemopreventive and anticancer activities. One of them is sulforaphene (SF), which is abundant in Rhapanus sativus seeds. The underlying mechanism of its anticancer activity is still underexplored. PURPOSE: SF properties make it an interesting candidate for cancer prevention and therapy. Thus, it is crucial to characterize the mechanism of its activity. STUDY DESIGN: We investigated the mechanism of antiproliferative activity of SF in breast cancer cells differing in growth factor receptors status and lacking functional p53...
June 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
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