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Cell Death Discovery

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https://www.readbyqxmd.com/read/28725491/ds16570511-is-a-small-molecule-inhibitor-of-the-mitochondrial-calcium-uniporter
#1
Naohiro Kon, Michiko Murakoshi, Aya Isobe, Katsuji Kagechika, Naoki Miyoshi, Takahiro Nagayama
In cardiac myocytes, regulation of mitochondrial Ca(2+) is important for cellular signaling and cardiac contraction. Ca(2+) entry into the mitochondria is mediated by a highly selective Ca(2+) channel called the mitochondrial calcium uniporter, which consists of a pore-forming subunit MCU and regulatory subunits such as MICU1. Although pharmacological regulation of the mitochondrial Ca(2+) influx is a promising approach to controlling the cellular functions, a cell-permeable and specific inhibitor of the mitochondrial calcium uniporter has not yet been developed...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28725490/muc1-o-glycosylation-contributes-to-anoikis-resistance-in-epithelial-cancer-cells
#2
Tushar Piyush, Jonathan M Rhodes, Lu-Gang Yu
Anoikis is a fundamental cellular process for maintaining tissue homeostasis. Resistance to anoikis is a hallmark of oncogenic epithelial-mesenchymal transition and is a pre-requisite for metastasis. Previous studies have revealed that the heavily glycosylated mucin protein MUC1, which is overexpressed in all types of epithelial cancer cells, prevents anoikis initiation in response to loss of adhesion. This effect of MUC1 is largely attributed to its extracellular domain that provides cell surface anoikis-initiating molecules with a 'homing' microenvironment...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28725489/bmp-2-induces-emt-and-breast-cancer-stemness-through-rb-and-cd44
#3
Peide Huang, Anan Chen, Weiyi He, Zhen Li, Guanglin Zhang, Zhong Liu, Ge Liu, Xueting Liu, Shuilian He, Gang Xiao, Feicheng Huang, Jan Stenvang, Nils Brünner, An Hong, Ju Wang
Bone morphogenetic protein 2 (BMP-2) has been reported to facilitate epithelial-to-mesenchymal transition (EMT) and bone metastasis in breast cancer xenograft models. To investigate the role of BMP-2 in the development of breast cancer stem cells (BCSCs), and to further elucidate the mechanisms underlying its influence on breast cancer metastasis, we conducted a comprehensive molecular study using breast cancer cell lines and clinical samples. Our results showed that downregulation of Rb by BMP-2 was associated with ubiquitin-mediated degradation activated by phosphorylation of Rb via the PI3K/AKT signal pathway...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28725488/generation-and-analysis-of-spheroids-from-human-primary-skin-myofibroblasts-an-experimental-system-to-study-myofibroblasts-deactivation
#4
Giuseppina Granato, Maria R Ruocco, Antonino Iaccarino, Stefania Masone, Gaetano Calì, Angelica Avagliano, Valentina Russo, Claudio Bellevicine, Gaetano Di Spigna, Giuseppe Fiume, Stefania Montagnani, Alessandro Arcucci
Myofibroblasts are activated fibroblasts involved in tissue repair and cancer. They are characterized by de novo expression of α-smooth muscle actin (α-SMA), immunoregulatory phenotype and paracrine interaction with normal and tumorigenic cells leading to cell proliferation. At the end of wound-healing myofibroblasts undergo apoptotic cell death, whereas in vitro-activated fibroblasts are also subjected to a programmed necrosis-like cell death, termed nemosis, associated with cyclooxygenase-2 (COX-2) expression induction and inflammatory response...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28698806/epigallocatechin-3-gallate-enhances-er-stress-induced-cancer-cell-apoptosis-by-directly-targeting-parp16-activity
#5
Juanjuan Wang, Chenggang Zhu, Dan Song, Ruiqi Xia, Wenbo Yu, Yongjun Dang, Yiyan Fei, Long Yu, Jiaxue Wu
Poly(ADP-ribose) polymerases (PARPs) are ADP-ribosylating enzymes and play important roles in a variety of cellular processes. Most small-molecule PARP inhibitors developed to date have been against PARP1, a poly-ADP-ribose transferase, and suffer from poor selectivity. PARP16, a mono-ADP-ribose transferase, has recently emerged as a potential therapeutic target, but its inhibitor development has trailed behind. Here we newly characterized epigallocatechin-3-gallate (EGCG) as a potential inhibitor of PARP16...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28698805/microrna-26a-inhibits-the-growth-and-invasiveness-of-malignant-melanoma-and-directly-targets-on-mitf-gene
#6
Hui Qian, Chen Yang, Yixin Yang
Metastatic melanoma is the most aggressive form of skin cancer and is refractory to therapy. MicroRNAs have been recently discovered as novel molecules that provide therapeutic benefits against melanoma. This work aims to examine the effects of miR-26a and let-7a on the growth and invasiveness of malignant melanoma in vitro and in vivo. In addition, we elucidate the mechanism of action by identifying the target gene of miR-26a. Both miR-26a and let-7a inhibited proliferation and invasiveness and halted the cell cycle at the G1/G0 phase in SKMEL-28 and WM1552C malignant melanoma cell lines...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28690875/combination-of-palbociclib-and-radiotherapy-for-glioblastoma
#7
Shane Whittaker, Daniel Madani, Swapna Joshi, Sylvia A Chung, Terrance Johns, Bryan Day, Mustafa Khasraw, Kerrie L McDonald
The cyclin-dependent kinase inhibitor, palbociclib has shown compelling efficacy in breast cancer patients. Several pre-clinical studies of glioblastoma (GBM) have also shown palbociclib to be efficacious. In this study, we investigated palbociclib in combination with radiation therapy (RT) for treating GBM. We tested palbociclib (with and without RT) on four patient-derived cell lines (PDCLs; RB1 retained; CDKN2A loss). We investigated the impact of therapy on the cell cycle and apoptosis using flow cytometry, in vitro...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28690874/sulforaphane-cysteine-induced-apoptosis-via-phosphorylated-erk1-2-mediated-maspin-pathway-in-human-non-small-cell-lung-cancer-cells
#8
Kai Lin, Ronghui Yang, Zhongnan Zheng, Yan Zhou, Yang Geng, Yabin Hu, Sai Wu, Wei Wu
Sulforaphane (SFN) was demonstrated to induce apoptosis in a variety of cancers via multiple mechanisms. However, owing to a short half-life in circulation, SFN was not used for clinical treatment yet. Interestingly, SFN analog, sulforaphane-cysteine (SFN-Cys) has a longer half-life in metabolism, and we previously demonstrated that SFN-Cys inhibited invasion in human prostate cancer cells. Here, we would investigate whether SFN-Cys induces apoptosis and find the underlying mechanisms in human non-small cell lung cancer (NSCLC) cells...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28660075/the-bile-acid-receptor-fxr-attenuates-acinar-cell-autophagy-in-chronic-pancreatitis
#9
Xiaodong Zhou, Li Xie, Frank Bergmann, Volker Endris, Oliver Strobel, Markus W Büchler, Guido Kroemer, Thilo Hackert, Franco Fortunato
The functional relationship between bile acid (BA) and autophagy has not been evaluated in the context of pancreatitis. Here we investigated whether BA and their nuclear farnesoid X receptor (FXR) modulate autophagy and the development of pancreatitis. FXR expression, autophagy, apoptosis and necroptosis were determined in human chronic pancreatitis (CP) tissue in vivo and in pancreatic cells lines in vitro by means of real-time PCR, immunoblots and immunofluorescence. Pancreatic cell lines exposed to the most abundant BAs glycochenodeoxycholate (GCDC) and taurocholic acid (TCA) increased the expression of nuclear FXR and diminished that of the essential autophagy-related protein ATG7...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28580175/differential-cytokine-withdrawal-induced-death-sensitivity-of-effector-t-cells-derived-from-distinct-human-cd8-memory-subsets
#10
Sasha E Larsen, Kelsey Voss, Eric D Laing, Andrew L Snow
CD8(+) central memory (CM) and effector memory (EM) T-cell subsets exhibit well-established differences in proliferative and protective capacity after infectious challenge. However, their relative sensitivity to apoptosis has been largely overlooked, despite the importance of programmed cell death in regulating effector T-cell homeostasis. Here we demonstrate that primary human effector T cells derived from the CD8(+) EM subset exhibit significantly higher sensitivity to cytokine withdrawal-induced cell death (CWID), a critical intrinsic apoptosis program responsible for culling cells once an infection is cleared and interleukin-2 (IL-2) levels diminish...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28580174/effects-of-concomitant-inactivation-of-p53-and-prb-on-response-to-doxorubicin-treatment-in-breast-cancer-cell-lines
#11
Johanna Huun, Per Eystein Lønning, Stian Knappskog
Loss of TP53 and RB1 function have both been linked to poor response to DNA damaging drugs in breast cancer patients. We inactivated TP53 and/or RB1 by siRNA mediated knockdown in breast cancer cell lines varying with respect to ER/PgR and Her-2 status as well as TP53 and RB1 mutation status (MCF-7, T47D, HTB-122 and CRL2324) and determined effects on cell cycle arrest, apoptosis and senescence with or without concomitant treatment with doxorubicin. In T47D cells, we found the cell cycle phase distribution to be altered when inactivating TP53 (P=0...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28580173/sesn2-gene-ablation-enhances-susceptibility-to-gentamicin-induced-hair-cell-death-via-modulation-of-ampk-mtor-signaling
#12
Eliane Ebnoether, Alessia Ramseier, Maurizio Cortada, Daniel Bodmer, Soledad Levano-Huaman
The process of gentamicin-induced hair cell damage includes the activation of oxidative stress processes. Sestrins, as stress-responsive proteins, protect cells against oxidative stress. Sestrins, particularly Sestrin-2, suppress excessive reactive oxygen species (ROS) accumulation and inhibit mammalian target of rapamycin complex 1 (mTORC1). Thus, we addressed the role of Sestrin-2 in the regulation of sensory hair cell survival after gentamicin exposure. Here, we show that Sestrins were expressed in the inner ear tissues, and Sestrin-2 immunolocalized in sensory hair cells and spiral ganglion (SG)...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28580172/ralbp1-and-p19-vhl-play-an-oncogenic-role-and-p30-vhl-plays-a-tumor-suppressor-role-during-the-blebbishield-emergency-program
#13
Goodwin G Jinesh, Ashish M Kamat
Cancer stem cells evade apoptotic death by blebbishield emergency program, which constructs blebbishields from apoptotic bodies and drives cellular transformation. Von Hippel-Lindau (VHL) plays both tumor suppressor and oncogenic roles, and the reason behind is poorly understood. Here we demonstrate that dimers and trimers of p19-VHL interact with RalBP1 to construct blebbishields. Expression of RalBP1, p19-VHL, and high-molecular weight VHL is required to evade apoptosis by blebbishield-mediated transformation...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28580171/in-silico-analysis-of-pathways-activation-landscape-in-oral-squamous-cell-carcinoma-and-oral-leukoplakia
#14
Eugene Makarev, Adrian D Schubert, Riya R Kanherkar, Nyall London, Mahder Teka, Ivan Ozerov, Ksenia Lezhnina, Atul Bedi, Rajani Ravi, Rannee Mehra, Mohammad O Hoque, Ido Sloma, Daria A Gaykalova, Antonei B Csoka, David Sidransky, Alex Zhavoronkov, Evgeny Izumchenko
A subset of patients with oral squamous cell carcinoma (OSCC), the most common subtype of head and neck squamous cell carcinoma (HNSCC), harbor dysplastic lesions (often visually identified as leukoplakia) prior to cancer diagnosis. Although evidence suggest that leukoplakia represents an initial step in the progression to cancer, signaling networks driving this progression are poorly understood. Here, we applied in silico Pathway Activation Network Decomposition Analysis (iPANDA), a new bioinformatics software suite for qualitative analysis of intracellular signaling pathway activation using transcriptomic data, to assess a network of molecular signaling in OSCC and pre-neoplastic oral lesions...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28580170/cell-free-chromatin-from-dying-cancer-cells-integrate-into-genomes-of-bystander-healthy-cells-to-induce-dna-damage-and-inflammation
#15
Indraneel Mittra, Urmila Samant, Suvarna Sharma, Gorantla V Raghuram, Tannistha Saha, Pritishkumar Tidke, Namrata Pancholi, Deepika Gupta, Preeti Prasannan, Ashwini Gaikwad, Nilesh Gardi, Rohan Chaubal, Pawan Upadhyay, Kavita Pal, Bhagyeshri Rane, Alfina Shaikh, Sameer Salunkhe, Shilpee Dutt, Pradyumna K Mishra, Naveen K Khare, Naveen K Nair, Amit Dutt
Bystander cells of the tumor microenvironment show evidence of DNA damage and inflammation that can lead to their oncogenic transformation. Mediator(s) of cell-cell communication that brings about these pro-oncogenic pathologies has not been identified. We show here that cell-free chromatin (cfCh) released from dying cancer cells are the key mediators that trigger both DNA damage and inflammation in the surrounding healthy cells. When dying human cancer cells were cultured along with NIH3T3 mouse fibroblast cells, numerous cfCh emerged from them and rapidly entered into nuclei of bystander NIH3T3 cells to integrate into their genomes...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28580169/endogenous-mirna-sponge-lincrna-ror-promotes-proliferation-invasion-and-stem-cell-like-phenotype-of-pancreatic-cancer-cells
#16
Zhiqiang Fu, Guolin Li, Zhihua Li, Yingxue Wang, Yue Zhao, Shangyou Zheng, Huilin Ye, Yuming Luo, Xiaohui Zhao, Lusheng Wei, Yimin Liu, Qing Lin, Quanbo Zhou, Rufu Chen
The long intergenic non-coding RNA, regulator of reprogramming (linc-ROR) is an oncogene and plays a key role in the embryonic stem cell maintenance and is involved in cancer progression. The objective of this study was to analyze linc-ROR expression in pancreatic ductal adenocarcinoma (PDAC) and determine the regulation effects of linc-ROR on proliferation and invasion of cancer cells, as well as properties of cancer stem-like cells (CSLCs). In this study, we found that linc-ROR was up-regulated in PDAC tissues and related to poor prognosis...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28580168/caml-mediates-survival-of-myc-induced-lymphoma-cells-independent-of-tail-anchored-protein-insertion
#17
Jennifer C Shing, Lonn D Lindquist, Nica Borgese, Richard J Bram
Calcium-modulating cyclophilin ligand (CAML) is an endoplasmic reticulum (ER) protein that functions, along with WRB and TRC40, to mediate tail-anchored (TA) protein insertion into the ER membrane. Physiologic roles for CAML include endocytic trafficking, intracellular calcium signaling, and the survival and proliferation of specialized immune cells, recently attributed to its requirement for TA protein insertion. To identify a possible role for CAML in cancer cells, we generated Eμ-Myc transgenic mice that carry a tamoxifen-inducible deletion allele of Caml...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28540063/microrna-122-ameliorates-corneal-allograft-rejection-through-the-downregulation-of-its-target-cpeb1
#18
Ting Wang, Fengjie Li, Wenwen Geng, Qingguo Ruan, Weiyun Shi
Transplant rejection is a major cause of corneal transplantation failure. MicroRNAs (miRNAs) are a family of small RNAs that regulates gene expression in a sequence-specific manner. miRNAs have recently been shown to have important roles in human organ transplantation, but reports of miRNAs directly associated with corneal transplantation rejection remain limited. To investigate the role of miRNAs during corneal allograft rejection, we established a mouse penetrating keratoplasty model and used microarrays to screen for differentially expressed miRNAs...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28496992/flavored-little-cigar-smoke-induces-cytotoxicity-and-apoptosis-in-airway-epithelia
#19
Arunava Ghosh, Rachel C Nethery, Amy H Herring, Robert Tarran
Addition of flavors reduces the harsh taste of tobacco, facilitating the initiation and maintenance of addiction among youths. Flavored cigarettes (except menthol) are now banned. However, the legislation on little cigars remains unclear and flavored little cigars are currently available for purchase. Since inhaled tobacco smoke directly exerts toxic effects on the lungs, we tested whether non-flavored and flavored little cigar smoke exposure had the potential for harm in cultured pulmonary epithelia. We cultured Calu-3 lung epithelia on both 96-well plates and at the air-liquid interface and exposed them to smoke from non-flavored Swisher Sweets and flavored (sweet cherry, grape, menthol, peach and strawberry) Swisher Sweets little cigars...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28487767/inducement-of-apoptosis-by-cucurbitacin-e-a-tetracyclic-triterpenes-through-death-receptor-5-in-human-cervical-cancer-cell-lines
#20
Ya-Min Cheng, Ching-Ju Shen, Chi-Chang Chang, Cheng-Yang Chou, Ching-Chou Tsai, Yi-Chiang Hsu
Cervical cancer is the most common malignancy in women, for which conization or hysterectomy are the main therapy. Curcubitacin E (Cu E) is a natural compound-based drug which from the Guadi (climbing stem of Cucumic melo L). Previously shown to be an anti-tumor as well as a potent chemopreventive agent against several types of tumors. The present study, investigated anti-proliferation and apoptosis induced by Cu E in cervical cancer cell lines (HeLa and Ca Ski). The results indicate that the cytotoxicity is associated with accumulation in apoptosis but not necrosis...
2017: Cell Death Discovery
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