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intrinsic apoptosis pathway

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https://www.readbyqxmd.com/read/28101573/combining-doxorubicin-with-a-phenolic-extract-from-flaxseed-oil-evaluation-of-the-effect-on-two-breast-cancer-cell-lines
#1
Eliana Guerriero, Angela Sorice, Francesca Capone, Gabriella Storti, Giovanni Colonna, Gennaro Ciliberto, Susan Costantini
Breast cancer is one of the most frequently diagnosed forms of cancer and different treatments are used to block its progression. However, it still represents a very common cause of death in women. Doxorubicin (Dox) is reported as an effective agent in breast cancer treatment nonetheless it induces many side‑effects. For this reason, many laboratories are engaged in understanding how it is possible to decrease the drug concentration, considering that one of the possible solutions is to use drug synergy, combining it with natural substances...
February 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28096658/anticancer-and-anti-inflammatory-activities-of-girinimbine-isolated-from-murraya-koenigii
#2
Venoos Iman, Syam Mohan, Siddig Ibrahim Abdelwahab, Hamed Karimian, Noraziah Nordin, Mehran Fadaeinasab, Mohamad Ibrahim Noordin, Suzita Mohd Noor
Therapy that directly targets apoptosis and/or inflammation could be highly effective for the treatment of cancer. Murraya koenigii is an edible herb that has been traditionally used for cancer treatment as well as inflammation. Here, we describe that girinimbine, a carbazole alkaloid isolated from M. koenigii, induced apoptosis and inhibited inflammation in vitro as well as in vivo. Induction of apoptosis in human colon cancer cells (HT-29) by girinimbine revealed decreased cell viability in HT-29, whereas there was no cytotoxic effect on normal colon cells...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28095907/the-targeted-smac-mimetic-sw-iv-134-is-a-strong-enhancer-of-standard-chemotherapy-in-pancreatic-cancer
#3
Yassar M Hashim, Suwanna Vangveravong, Narendra V Sankpal, Pratibha S Binder, Jingxia Liu, S Peter Goedegebuure, Robert H Mach, Dirk Spitzer, William G Hawkins
BACKGROUND: Pancreatic cancer is a lethal malignancy that frequently acquires resistance to conventional chemotherapies often associated with overexpression of inhibitors of apoptosis proteins (IAPs). We have recently described a novel means to deliver second mitochondria-derived activator of caspases (SMAC) mimetics selectively to cancer cells employing the sigma-2 ligand/receptor interaction. The intrinsic death pathway agonist SMAC offers an excellent opportunity to counteract the anti-apoptotic activity of IAPs...
January 17, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28095346/crystal-structure-cytotoxicity-and-action-mechanism-of-zn-ii-mn-ii-complexes-with-isoquinoline-ligands
#4
Feng-Yang Wang, Qian-Yu Xi, Ke-Bin Huang, Xiao-Ming Tang, Zhen-Feng Chen, Yan-Cheng Liu, Hong Liang
Four μ2-Cl bridged dinuclear metal complexes with isoquinoline ligands, (MPDQ)2Zn2Cl4 (1) (MPDQ=4.5-methylenedioxy-1-pyridinedihydroisoquinoline), (PYP)2Zn2Cl4 (2) (PYP=5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline), (MPDQ)2Mn2Cl4 (3),and (PYP)2Mn2Cl4 (4) were synthesized and characterized. All complexes exhibited strong proliferation inhibition activity against various cancer cells. The underlying molecular mechanisms through which they caused the cancer cell death were also elucidated. Induction of apoptosis in MGC-803 cells by complex 2 was evidenced by annexin V(+)/PI(-) detection and DiD/DAPI staining assay...
January 6, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28094536/the-novel-induction-of-retinal-ganglion-cell-apoptosis-in-porcine-organ-culture-by-nmda-an-opportunity-for-the-replacement-of-animals-in-experiments
#5
Sandra Kuehn, Jose Hurst, Adelina Jashari, Kathrin Ahrens, Teresa Tsai, Ilan M Wunderlich, H Burkhard Dick, Stephanie C Joachim, Sven Schnichels
Some of the advantages of retina organ culture models include their efficient and easy handling and the ability to standardise relevant parameters. Additionally, when porcine eyes are obtained from the food industry, no animals are killed solely for research purposes. To induce retinal degeneration, a commonly used toxic substance, N-methyl-D-aspartate (NMDA), was applied to the cultures. To this end, organotypic cultures of porcine retinas were cultured and treated with different doses of NMDA (0 [control], 50, 100 and 200μM) on day 2 for 48 hours...
December 2016: Alternatives to Laboratory Animals: ATLA
https://www.readbyqxmd.com/read/28092373/chronic-signaling-via-the-metabolic-checkpoint-kinase-mtorc1-induces-macrophage-granuloma-formation-and-marks-sarcoidosis-progression
#6
Monika Linke, Ha Thi Thanh Pham, Karl Katholnig, Thomas Schnöller, Anne Miller, Florian Demel, Birgit Schütz, Margit Rosner, Boris Kovacic, Nyamdelger Sukhbaatar, Birgit Niederreiter, Stephan Blüml, Peter Kuess, Veronika Sexl, Mathias Müller, Mario Mikula, Wolfram Weckwerth, Arvand Haschemi, Martin Susani, Markus Hengstschläger, Michael J Gambello, Thomas Weichhart
The aggregation of hypertrophic macrophages constitutes the basis of all granulomatous diseases, such as tuberculosis or sarcoidosis, and is decisive for disease pathogenesis. However, macrophage-intrinsic pathways driving granuloma initiation and maintenance remain elusive. We found that activation of the metabolic checkpoint kinase mTORC1 in macrophages by deletion of the gene encoding tuberous sclerosis 2 (Tsc2) was sufficient to induce hypertrophy and proliferation, resulting in excessive granuloma formation in vivo...
January 16, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28089818/notochordal-cell-derived-conditioned-medium-nccm-protects-human-nucleus-pulposus-cells-from-stress-induced-apoptosis
#7
Arne Mehrkens, Ajay Matta, M Zia Karim, Sarah Kim, Michael G Fehlings, Stefan Schaeren, W Mark Erwin
BACKGROUND CONTEXT: Degenerative Disc Disease (DDD) remains without an effective therapy and presents a costly burden to society. PURPOSE: Based upon prior reports concerning the effects of notochordal cell conditioned medium (NCCM) upon disc cells, we performed a proof of principle study to determine whether NCCM could reduce cytotoxic stress induced apoptosis in human disc nucleus pulpous (NP) cells. STUDY DESIGN/SETTING: 'in vitro' fundamental/basic science study METHODS: NP cells derived from 15 patients undergoing spinal surgery were treated with interleukin 1β (IL-1β) and Fas ligand (FasL) or etoposide in the presence of NCCM...
January 9, 2017: Spine Journal: Official Journal of the North American Spine Society
https://www.readbyqxmd.com/read/28088793/hnrnp-l-mediates-bladder-cancer-progression-by-inhibiting-apoptotic-signaling-and-enhancing-mapk-signaling-pathways
#8
Daojun Lv, Huayan Wu, Rongwei Xing, Fangpeng Shu, Bin Lei, Chengyong Lei, Xumin Zhou, Bo Wan, Yu Yang, Liren Zhong, Xiangming Mao, Yaguang Zou
Heterogeneous nuclear ribonucleoprotein L (hnRNP-L) is a promoter of various kinds of cancers, but its actions in bladder cancer (BC) are unclear. In this study, we investigated the function and the underlying mechanism of hnRNP-L in bladder carcinogenesis. Our results demonstrated that enhanced hnRNP-L expression in BC tissues was associated with poor overall survival of BC patients. Depletion of hnRNP-L significantly suppressed cell proliferation in vitro and inhibited xenograft tumor growth in vivo. Furthermore, downregulation of hnRNP-L resulted in G1-phase cell cycle arrest and enhanced apoptosis accompanied by inhibition of EMT and cell migration...
January 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088539/the-dna-damage-response-of-c-elegans-affected-by-gravity-sensing-and-radiosensitivity-during-the-shenzhou-8-spaceflight
#9
Ying Gao, Dan Xu, Lei Zhao, Yeqing Sun
Space radiation and microgravity are recognized as primary and inevitable risk factors for humans traveling in space, but the reports regarding their synergistic effects remain inconclusive and vary across studies due to differences in the environmental conditions and intrinsic biological sensitivity. Thus, we studied the synergistic effects on transcriptional changes in the global genome and DNA damage response (DDR) by using dys-1 mutant and ced-1 mutant of C. elegans, which respectively presented microgravity-insensitivity and radiosensitivity when exposure to spaceflight condition (SF) and space radiation (SR)...
January 7, 2017: Mutation Research
https://www.readbyqxmd.com/read/28088077/rhoa-knockdown-by-cationic-amphiphilic-copolymer-sirhoa-polyplexes-enhances-axonal-regeneration-in-rat-spinal-cord-injury-model
#10
So-Jung Gwak, Christian Macks, Da Un Jeong, Mark Kindy, Michael Lynn, Ken Webb, Jeoung Soo Lee
Spinal cord injury (SCI) results in permanent loss of motor and sensory function due to developmentally-related and injured-induced changes in the extrinsic microenvironment and intrinsic neuronal biochemistry that limit plasticity and axonal regeneration. Our long term goal is to develop cationic, amphiphilic copolymers (poly (lactide-co-glycolide)-g-polyethylenimine, PgP) for combinatorial delivery of therapeutic nucleic acids (TNAs) and drugs targeting these different barriers. In this study, we evaluated the ability of PgP to deliver siRNA targeting RhoA, a critical signaling pathway activated by multiple extracellular inhibitors of axonal regeneration...
January 3, 2017: Biomaterials
https://www.readbyqxmd.com/read/28078580/in-vitro-evaluation-of-the-apoptosis-function-in-human-activated-t-cells
#11
Aude Magerus-Chatinet, Frédéric Rieux-Laucat
The apoptosis function can be monitored on human lymphocytes by quantifying the induced-death upon apoptotic stimuli involving either the extrinsic or the intrinsic pathway on in vitro activated T cells. Her, we describe an in vitro assay allowing the monitoring of three different apoptosis pathways: (1) the FAS-induced pathway, (2) the activation-induced cell death (AICD), and (3) the death induced by starvation of the cells, called activated-cell autonomous death (ACAD).
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28075477/escin-induces-apoptosis-in-human-renal-cancer-cells-through-g2-m-arrest-and-reactive-oxygen-species-modulated-mitochondrial-pathways
#12
Sheau-Yun Yuan, Chen-Li Cheng, Shian-Shiang Wang, Hao-Chung Ho, Kun-Yuan Chiu, Chuan-Shu Chen, Cheng-Che Chen, Ming-Yuh Shiau, Yen-Chuan Ou
Escin, a natural pentacyclic triterpenoid compound, exhibits antitumor effects on various types of human cancer cells, but its effect on human renal cancer cells has not been fully elucidated. In the present study, we demonstrated that escin elicits cytotoxic effects on human renal cancer cells (786-O and Caki-1) in a dose-dependent manner, as determined by MTT assay. Escin induced G2/M arrest, and then increased the sub-G1 population, Annexin V binding, activation of caspase-9/-3, cleavage of poly(ADP-ribose) polymerase (PARP) and Bax protein...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/28073829/dutpase-dut-is-mutated-in-a-novel-monogenic-syndrome-with-diabetes-and-bone-marrow-failure
#13
Reinaldo Sousa Dos Santos, Mathilde Daures, Anne Philippi, Sophie Romero, Lorella Marselli, Piero Marchetti, Valérie Senée, Delphine Bacq, Céline Besse, Baz Baz, Laura Marroquí, Sarah Ivanoff, Julien Masliah-Planchon, Marc Nicolino, Jean Soulier, Gérard Socié, Decio L Eizirik, Jean-François Gautier, Cécile Julier
We describe a new syndrome characterized by early onset diabetes mellitus, associated with bone marrow failure affecting mostly the erythrocytic lineage. Using whole exome sequencing in a remotely consanguineous patient from a family with two affected siblings, we identified a single homozygous missense mutation (chr15.hg19:g.48,626,619A>G) located in the dUTPase (DUT) gene (NCBI Gene ID: 1854), affecting both the mitochondrial (DUT-M p.Y142C) and the nuclear (DUT-N p.Y54C) isoforms. We found the same homozygous mutation in an unrelated consanguineous patient with diabetes and bone marrow aplasia from a family with two affected siblings, while none of the >60,000 subjects from the Exome Aggregation Consortium (ExAC) was homozygous for this mutation...
January 10, 2017: Diabetes
https://www.readbyqxmd.com/read/28072603/dyserythropoiesis-of-myelodysplastic-syndromes
#14
Carine Lefèvre, Sabrina Bondu, Salomé Le Goff, Olivier Kosmider, Michaela Fontenay
PURPOSE OF REVIEW: Myelodysplastic syndromes (MDS) are heterogeneous diseases of the hematopoietic stem cell in the elderly. Anemia is the main symptom that mostly correlates with dysplastic erythropoiesis in the bone marrow. We will review the recent advances in understanding the diverse mechanisms of dyserythropoiesis. RECENT FINDINGS: Dyserythropoiesis defined as 10% dysplastic erythroid cells in the bone marrow is found in more than 80% of early MDS. Immature erythroblasts accumulate at the expense of mature erythroblasts due to differentiation arrest and apoptosis...
January 7, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28070612/macrolide-antibiotics-differentially-influence-human-hepg2-cytotoxicity-and-modulate-intrinsic-extrinsic-apoptotic-pathways-in-rat-hepatocellular-carcinoma-model
#15
Nagwa I Abdel-Hamid, Mona F El-Azab, Yasser M Moustafa
This study was designed to examine the potential antitumor effect of some macrolides: clarithromycin, azithromycin, and erythromycin on chemically induced hepatocellular carcinoma (HCC) in rats and on human hepatoma cells (HepG2) as well. The possible underlying antiapoptotic mechanisms were investigated. Antiproliferative activity was assessed in HepG2 using Sulforhodamine-B staining method. In vivo, HCC was induced in rats by initiation-selection-promotion protocol using diethylnitrosamine (200 mg/kg, single i...
January 9, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28067803/regulation-of-viral-replication-apoptosis-and-pro-inflammatory-responses-by-17-aag-during-chikungunya-virus-infection-in-macrophages
#16
Tapas K Nayak, Prabhudutta Mamidi, Abhishek Kumar, Laishram Pradeep K Singh, Subhransu S Sahoo, Soma Chattopadhyay, Subhasis Chattopadhyay
Chikungunya virus (CHIKV) infection has re-emerged as a major public health concern due to its recent worldwide epidemics and lack of control measures. Although CHIKV is known to infect macrophages, regulation of CHIKV replication, apoptosis and immune responses towards macrophages are not well understood. Accordingly, the Raw264.7 cells, a mouse macrophage cell line, were infected with CHIKV and viral replication as well as new viral progeny release was assessed by flow cytometry and plaque assay, respectively...
January 6, 2017: Viruses
https://www.readbyqxmd.com/read/28067213/metallic-copper-nanoparticle-induces-apoptosis-in-human-skin-melanoma-a-375-cell-line
#17
Ruchira Chakraborty, Tarakdas Basu
In earlier two communications [Chatterjee et al., 2012; Chatterjee et al., 2014], we reported to develop a simple and unique method of synthesis of highly stable metallic copper nanoparticle (Cu-NP) with high antibacterial potency. Here we report about the cytotoxic potency of the NP against cancer cells. The value of the IC50 dose of the Cu-NP against human skin cancer cell A-375 was found to be 1.71��g/ml only, which was much less than the values reported so far and this concentration had no cytotoxic effect on normal WBC...
January 9, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28064040/bax-to-basics-how-the-bcl2-gene-family-controls-the-death-of-retinal-ganglion-cells
#18
REVIEW
Margaret E Maes, Cassandra L Schlamp, Robert W Nickells
Retinal ganglion cell (RGC) death is the principal consequence of injury to the optic nerve. For several decades, we have understood that the RGC death process was executed by apoptosis, suggesting that there may be ways to therapeutically intervene in this cell death program and provide a more direct treatment to the cells and tissues affected in diseases like glaucoma. A major part of this endeavor has been to elucidate the molecular biological pathways active in RGCs from the point of axonal injury to the point of irreversible cell death...
January 4, 2017: Progress in Retinal and Eye Research
https://www.readbyqxmd.com/read/28060382/epigenetic-control-of-mitochondrial-cell-death-through-pacs1-mediated-regulation-of-bax-bak-oligomerization
#19
Daniella Brasacchio, Amber E Alsop, Tahereh Noori, Mariam Lufti, Sweta Iyer, Kaylene J Simpson, Phillip I Bird, Ruth M Kluck, Ricky W Johnstone, Joseph A Trapani
PCAF and ADA3 associate within the same macromolecular complexes to control the transcription of many genes, including some that regulate apoptosis. Here we show that PCAF and ADA3 regulate the expression of PACS1, whose protein product is a key component of the machinery that sorts proteins among the trans-Golgi network and the endosomal compartment. We describe a novel role for PACS1 as a regulator of the intrinsic pathway of apoptosis and mitochondrial outer membrane permeabilization. Cells with decreased PACS1 expression were refractory to cell death mediated by a variety of stimuli that operate through the mitochondrial pathway, including human granzyme B, staurosporine, ultraviolet radiation and etoposide, but remained sensitive to TRAIL receptor ligation...
January 6, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28053194/mir-125b-promotes-mll-af9-driven-murine-acute-myeloid-leukemia-involving-a-vegfa-mediated-non-cell-intrinsic-mechanism
#20
Jun Liu, Bo Guo, Zhuo Chen, Nayi Wang, Michelina Iacovino, Jijun Cheng, Christine Roden, Wen Pan, Sajid Khan, Suning Chen, Michael Kyba, Rong Fan, Shangqin Guo, Jun Lu
The hematopoietic-stem-cell-enriched miR-125-family miRNAs are critical regulators of hematopoiesis. Overexpression of miR-125a or miR-125b are frequent in human acute myeloid leukemia (AML), and their overexpression in mice leads to expansion of hematopoietic stem cells accompanied by perturbed hematopoiesis with mostly myeloproliferative phenotypes. However, whether and how miR-125 family miRNAs cooperate with known AML oncogenes in vivo, and how the resultant leukemia is dependent on miR-125 overexpression is not well understood...
January 4, 2017: Blood
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