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https://read.qxmd.com/read/30850585/inhibition-of-pink1-parkin-dependent-mitophagy-sensitizes-multidrug-resistant-cancer-cells-to-b5g1-a-new-betulinic-acid-analog
#1
Nan Yao, Chenran Wang, Nan Hu, Yingjie Li, Mingqun Liu, Yuhe Lei, Minfeng Chen, Liping Chen, Chen Chen, Ping Lan, Weimin Chen, Zhesheng Chen, Dengrui Fu, Wencai Ye, Dongmei Zhang
Betulinic acid (BA) and its derivatives are a class of high-profile drug candidates, but their anticancer effects on resistant cancer have rarely been reported. Although a few studies indicated mitophagy is related with drug resistance, its role in different cancer types and anticancer agents treatment remains largely unclear. Here, we find that B5G1, a new derivative of BA, induces cell death in multidrug resistant cancer cells HepG2/ADM and MCF-7/ADR through mitochondrial-apoptosis pathway. B5G1 also triggers mitophagy independent on Atg5/Beclin 1...
March 8, 2019: Cell Death & Disease
https://read.qxmd.com/read/30612517/vitamin-d3-activates-the-autolysosomal-degradation-function-against-helicobacter-pylori-through-the-pdia3-receptor-in-gastric-epithelial-cells
#2
Wei Hu, Lin Zhang, Ming Xing Li, Jing Shen, Xiao Dong Liu, Zhan Gang Xiao, Ding Lan Wu, Idy H T Ho, Justin C Y Wu, Cynthia K Y Cheung, Yu Chen Zhang, Alaster H Y Lau, Hassan Ashktorab, Duane T Smoot, Evandro F Fang, Matthew T V Chan, Tony Gin, Wei Gong, William K K Wu, Chi Hin Cho
Helicobacter pylori (H. pylori) is a common human pathogenic bacterium. Once infected, it is difficult for the host to clear this organism using the innate immune system. Increased antibiotic resistance further makes it challenging for effective eradication. However, the mechanisms of immune evasion still remain obscure, and novel strategies should be developed to efficiently eliminate H. pylori infection in stomachs. Here we uncovered desirable anti-H. pylori effect of vitamin D3 both in vitro and in vivo, even against antibiotic-resistant strains...
January 6, 2019: Autophagy
https://read.qxmd.com/read/30553871/endoplasmic-reticulum-stress-triggered-by-soyasapogenol-b-promotes-apoptosis-and-autophagy-in-colorectal-cancer
#3
Luping Wang, Lu Yun, Xiaojun Wang, Liying Sha, Luning Wang, Yingying Sui, Hui Zhang
AIM: Colorectal cancer (CRC) is a common human malignancy which accounts for 600,000 deaths annually at the global level. Soyasapogenol B (Soy B), an ingredient of soybean, has been found to exert anti-proliferative activities in vitro in human breast cancer cells. The current study aimed to evaluate the efficacy of Soy B in suppressing CRC. METHODS AND MATERIALS: The effect of Soy B on cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay. The effect of Soy B on cell proliferation was determined using colony formation assay...
December 13, 2018: Life Sciences
https://read.qxmd.com/read/30513588/the-er-stress-inducer-l-azetidine-2-carboxylic-acid-elevates-the-levels-of-phospho-eif2%C3%AE-and-of-lc3-ii-in-a-ca-2-dependent-manner
#4
Gemma Roest, Evelien Hesemans, Kirsten Welkenhuyzen, Tomas Luyten, Nikolai Engedal, Geert Bultynck, Jan B Parys
Accumulation of misfolded proteins in the endoplasmic reticulum (ER) activates the unfolded protein response (UPR) to reduce protein load and restore homeostasis, including via induction of autophagy. We used the proline analogue l-azetidine-2-carboxylic acid (AZC) to induce ER stress, and assessed its effect on autophagy and Ca2+ homeostasis. Treatment with 5 mM AZC did not induce poly adenosine diphosphate ribose polymerase (PARP) cleavage while levels of binding immunoglobulin protein (BiP) and phosphorylated eukaryotic translation initiation factor 2α (eIF2α) increased and those of activating transcription factor 6 (ATF6) decreased, indicating activation of the protein kinase RNA-like ER kinase (PERK) and the ATF6 arms of the UPR but not of apoptosis...
November 30, 2018: Cells
https://read.qxmd.com/read/30416757/autophagy-modulates-temozolomide-induced-cell-death-in-alveolar-rhabdomyosarcoma-cells
#5
Adel Rezaei Moghadam, Simone C da Silva Rosa, Ehsan Samiei, Javad Alizadeh, Jared Field, Philip Kawalec, James Thliveris, Mohsen Akbari, Saeid Ghavami, Joseph W Gordon
Rhabdomyosarcoma (RMS) is a muscle-derived tumor. In both pre-clinical and clinical studies Temozolomide (TMZ) has been recently tested against RMS; however, the precise mechanism of action of TMZ in RMS remains unclear. Here we demonstrate that TMZ decreases the cell viability of the RH30 RMS and C2C12 cell line, where cells display evidence of mitochondrial outer membrane permeability. Interestingly, the C2C12 mouse myoblast line was relatively more resistant to TMZ-induced apoptosis. Moreover, we observed that TMZ activated biochemical and morphological markers of autophagy in both cell lines...
2018: Cell Death Discovery
https://read.qxmd.com/read/29988039/glutathione-depletion-induces-ferroptosis-autophagy-and-premature-cell-senescence-in-retinal-pigment-epithelial-cells
#6
Yun Sun, Yingfeng Zheng, Chunxiao Wang, Yizhi Liu
Glutathione (GSH) protects against oxidative damage in many tissues, including retinal pigment epithelium (RPE). Oxidative stress-mediated senescence and death of RPE and subsequent death of photoreceptors have been observed in age-related macular degeneration (AMD). Although the consequences of GSH depletion have been described previously, questions remain regarding the molecular mechanisms. We herein examined the downstream effects of GSH depletion on stress-induced premature senescence (SIPS) and cell death in human RPE cells...
July 9, 2018: Cell Death & Disease
https://read.qxmd.com/read/29770446/anticancer-activity-of-tetrandrine-by-inducing-pro-death-apoptosis-and-autophagy-in-human-gastric-cancer-cells
#7
Xin-Yu Bai, Yuan-Gui Liu, Wu Song, Ying-Ying Li, Dong-Shun Hou, Hao-Ming Luo, Ping Liu
OBJECTIVES: To investigate the antitumour property of tetrandrine by inducing autophagy and apoptosis in human gastric cancer cells, and to explore the potential molecular mechanisms. METHODS: The antitumour activity of tetrandrine was assessed through MTT assay. Apoptosis was measured by flow cytometry and microscopic examination of cellular morphology. The mitochondrial membrane potential was detected by staining with Rh-123. Induction of autophagy was monitored by transmission electron microscopy observation, using GFP-LC3 transfection...
August 2018: Journal of Pharmacy and Pharmacology
https://read.qxmd.com/read/28428261/ebf2-transcriptionally-regulates-brown-adipogenesis-via-the-histone-reader-dpf3-and-the-baf-chromatin-remodeling-complex
#8
Suzanne N Shapira, Hee-Woong Lim, Sona Rajakumari, Alexander P Sakers, Jeff Ishibashi, Matthew J Harms, Kyoung-Jae Won, Patrick Seale
The transcription factor early B-cell factor 2 (EBF2) is an essential mediator of brown adipocyte commitment and terminal differentiation. However, the mechanisms by which EBF2 regulates chromatin to activate brown fat-specific genes in adipocytes were unknown. ChIP-seq (chromatin immunoprecipitation [ChIP] followed by deep sequencing) analyses in brown adipose tissue showed that EBF2 binds and regulates the activity of lineage-specific enhancers. Mechanistically, EBF2 physically interacts with the chromatin remodeler BRG1 and the BAF chromatin remodeling complex in brown adipocytes...
April 1, 2017: Genes & Development
https://read.qxmd.com/read/27956235/valproic-acid-protects-against-mpp-mediated-neurotoxicity-in-sh-sy5y-cells-through-autophagy
#9
Y Zhang, J Y Wu, L H Weng, X X Li, L J Yu, Y Xu
Autophagy is a common physiological activity in cells. Studies show that dysregulation of autophagy is involved in the pathogenesis of Parkinson's disease (PD). As a commonly used anti-epileptic drug, valproic acid (VPA) has shown neuroprotective effects in PD. The aim of this study was to explore whether the autophagy induced by VPA involved in the neuroprotective effects in PD cell model. We found that VPA treatment counteracted MPP+ -caused autophagic flux impairment. Forthermore, VPA could alleviates apoptosis, reduce reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) loss caused by MPP+ ...
January 18, 2017: Neuroscience Letters
https://read.qxmd.com/read/27560771/inhibiting-autophagy-increases-epirubicin-s-cytotoxicity-in-breast-cancer-cells
#10
Wei Guo, Yu Wang, Zhu Wang, Yan-Ping Wang, Hong Zheng
Chemotherapy, radiotherapy, and endocrinotherapy are documented to induce autophagy among breast cancer cells, but the role of autophagy in this disease has been attributed as cytoprotective as well as tumor-suppressing. Thus we studied MDA-MB-231 and SK-BR-3 breast cancer cell lines treated with epirubicin (EPI) to assess autophagy and apoptosis. We found out that EPI induced apoptosis and autophagy in both cell lines. The lysosomal inhibitor bafilomycin A1 inhibited cellular autophagy and enhanced EPI-triggered apoptosis, perhaps due to inhibition of autolysosome formation, which then inhibited autophagic effects of engulfing and clearing damaged mitochondria...
November 2016: Cancer Science
https://read.qxmd.com/read/27340138/polydatin-post-treatment-alleviates-myocardial-ischaemia-reperfusion-injury-by-promoting-autophagic-flux
#11
Yuanna Ling, Guiming Chen, Yi Deng, Huixiong Tang, Long Ling, Xiaoming Zhou, Xudong Song, Pingzhen Yang, Yingfeng Liu, Zhiliang Li, Cong Zhao, Yufei Yang, Xianbao Wang, Masafumi Kitakaze, Yulin Liao, Aihua Chen
Polydatin (PD), a resveratrol (RES) glycoside, has a stronger antioxidative effect than RES. It is known that RES is an autophagic enhancer and exerts a cardioprotective effect against ischaemia/reperfusion (I/R) injury. However, the effect of PD post-treatment on myocardial I/R injury remains unclear. In the present study, we investigated the influences of PD post-treatment on myocardial I/R injury and autophagy. C57BL/6 mice underwent left coronary artery (LCA) occlusion and cultured neonatal rat cardiomyocytes (NRCs) subjected to hypoxia were treated with vehicle or PD during reperfusion or re-oxygenation...
September 1, 2016: Clinical Science (1979-)
https://read.qxmd.com/read/27129900/species-delimitation-phylogeny-and-evolutionary-demography-of-co-distributed-montane-frogs-in-the-southern-brazilian-atlantic-forest
#12
Carina R Firkowski, Marcos R Bornschein, Luiz F Ribeiro, Marcio R Pie
The Brazilian Atlantic Forest (BAF) is recognized as one of the world's biodiversity hotspots, with even more species per unit of area than the Amazon, however the mechanisms that led to such astonishing diversity are yet to be fully understood. In this study, we investigate the diversification of two co-distributed frog genera associated with montane areas of southern BAF: Melanophryniscus (Bufonidae) and Brachycephalus (Brachycephalidae). Species delimitation methods using mitochondrial and nuclear loci supported the existence of a remarkable number of highly endemic species in each genus, most of which occupy only one or a few adjacent mountaintops...
July 2016: Molecular Phylogenetics and Evolution
https://read.qxmd.com/read/25891311/silibinin-a-natural-flavonoid-induces-autophagy-via-ros-dependent-mitochondrial-dysfunction-and-loss-of-atp-involving-bnip3-in-human-mcf7-breast-cancer-cells
#13
Kai Jiang, Wei Wang, Xin Jin, Zhaoyang Wang, Zhiwei Ji, Guanmin Meng
Silibinin, derived from the milk thistle plant (Silybum marianum), has anticancer and chemopreventive properties. Silibinin has been reported to inhibit the growth of various types of cancer cells. However, the mechanisms by which silibinin exerts an anticancer effect are poorly defined. The present study aimed to investigate whether silibinin-induced cell death might be attributed to autophagy and the underlying mechanisms in human MCF7 breast cancer cells. Our results showed that silibinin-induced cell death was greatly abrogated by two specific autophagy inhibitors, 3-methyladenine (3-MA) and bafilomycin-A1 (Baf-A1)...
June 2015: Oncology Reports
https://read.qxmd.com/read/25572129/role-of-c-jun-n-terminal-kinase-activation-in-apoptosis-induced-by-removal-of-the-growth-factors
#14
Yue-Bao Ning, Zhi-Qiang Du
Apoptosis plays a crucial role for generation of lymphocyte repertoire, clonal contraction, and elimination of virus-infected cells. Since IL-3-dependent pro-B cell line Baf-3 resulted in rapid induction of apoptotic cell death upon IL-3 withdrawal, it would by very valuable for analysis of apoptosis induction by growth factor deprivation. First, we confirmed that Baf-3 cells underwent loss of mitochondrial membrane potential (ΔΨm) and apoptosis in a time-dependent manner when they were cultured in the RPMI-1640 medium without IL-3...
May 2015: Cell Biology International
https://read.qxmd.com/read/24291354/a-possible-role-of-transglutaminase-2-in-the-nucleus-of-ins-1e-and-of-cells-of-human-pancreatic-islets
#15
Sara Sileno, Valentina D'Oria, Riccardo Stucchi, Massimo Alessio, Stefania Petrini, Valentina Bonetto, Pierre Maechler, Federico Bertuzzi, Valeria Grasso, Katia Paolella, Fabrizio Barbetti, Ornella Massa
UNLABELLED: Transglutaminase 2 (TG2) is a multifunctional protein with Ca(2+)-dependent transamidating and G protein activity. Previously we reported that the role of TG2 in insulin secretion may involve cytoplasmic actin remodeling and a regulative action on other proteins during granule movement. The aim of this study was to gain a better insight into the role of TG2 transamidating activity in mitochondria and in the nucleus of INS-1E rat insulinoma cell line (INS-1E) during insulin secretion...
January 16, 2014: Journal of Proteomics
https://read.qxmd.com/read/24231740/caspase-inhibition-augments-dichlorvos-induced-dopaminergic-neuronal-cell-death-by-increasing-ros-production-and-parp1-activation
#16
W Y Wani, A Sunkaria, D R Sharma, R J L Kandimalla, A Kaushal, E Gerace, A Chiarugi, K D Gill
Numerous epidemiological studies have shown an association between pesticide exposure and the increased risk of developing Parkinson's disease. Previously we have reported that Dichlorvos exposure can induce oxidative stress, resulting in over-expression of pro-apoptotic genes and finally caspase-dependent nigrostriatal dopaminergic neuronal cell death in rat brain. Here, we examined the effect of caspase inhibition on PC12 cell death induced by Dichlorvos (30 μM). Reactive oxygen species (ROS) generation followed by protein carbonylation, lipid peroxidation, decreased antioxidant defenses (decreased Mn-superoxide dismutase (MnSOD) activity and decreased glutathione levels) and subsequent caspase activation mediated the apoptosis...
January 31, 2014: Neuroscience
https://read.qxmd.com/read/23577025/differential-cytotoxicity-responses-by-dog-and-rat-hepatocytes-to-phospholipogenic-treatments
#17
James K Morelli, Paul J Ciaccio
Dog and rat hepatocytes were treated with phospholipogenics to identify the more sensitive species and to determine whether lysosomal or mitochondrial changes were the primary cause of cytotoxicity. Endpoints included cell death, lysosome membrane integrity, mitochondrial membrane polarization, and fluorescent phospholipid (NBD-PE). Dog cells exhibited lower survival IC50 values than did rat cells with all phospholipogenic treatments and exhibited a lower capacity to accumulate NBD-PE in 4 of 5 phospholipogenic test conditions...
2013: Journal of Toxicology
https://read.qxmd.com/read/22943412/bafilomycin-a1-activates-hif-dependent-signalling-in-human-colon-cancer-cells-via-mitochondrial-uncoupling
#18
Alexander V Zhdanov, Ruslan I Dmitriev, Dmitri B Papkovsky
Mitochondrial uncoupling is implicated in many patho(physiological) states. Using confocal live cell imaging and an optical O2 sensing technique, we show that moderate uncoupling of the mitochondria with plecomacrolide Baf (bafilomycin A1) causes partial depolarization of the mitochondria and deep sustained deoxygenation of human colon cancer HCT116 cells subjected to 6% atmospheric O2. A decrease in iO2 (intracellular O2) to 0-10 μM, induced by Baf, is sufficient for stabilization of HIFs (hypoxia inducible factors) HIF-1α and HIF-2α, coupled with an increased expression of target genes including GLUT1 (glucose transporter 1), HIF PHD2 (prolyl hydroxylase domain 2) and CAIX (carbonic anhydrase IX)...
December 2012: Bioscience Reports
https://read.qxmd.com/read/22705646/the-vascular-targeting-agent-combretastatin-a4-directly-induces-autophagy-in-adenocarcinoma-derived-colon-cancer-cells
#19
Lisa M Greene, Niamh M O'Boyle, Derek P Nolan, Mary J Meegan, Daniela M Zisterer
Recent clinical data demonstrated that the vascular targeting agent Combretastatin-A4 phosphate (CA-4P) prolonged survival of patients with advanced anaplastic thyroid cancer without any adverse side effects. However, as a single agent CA-4 failed to reduce tumour growth in the murine CT-26 adenocarcinoma colon cancer model. Furthermore, the molecular mechanism of the innate resistance of HT-29 human adenocarcinoma cells to CA-4 is largely unknown. In this report, we demonstrate for the first time that prolonged exposure to CA-4 and an azetidinone cis-restricted analogue, CA-432 (chemical name; 4-(3-Hydroxy-4-methoxyphenyl)-3-phenyl-1-(3,4,5-trimethoxyphenyl)-azetidin-2-one) induced autophagy in adenocarcinoma-derived CT-26, Caco-2 and HT-29 cells but not in fibrosarcoma-derived HT-1080 cells...
September 1, 2012: Biochemical Pharmacology
https://read.qxmd.com/read/20820851/bafilomycin-a1-activates-respiration-of-neuronal-cells-via-uncoupling-associated-with-flickering-depolarization-of-mitochondria
#20
Alexander V Zhdanov, Ruslan I Dmitriev, Dmitri B Papkovsky
Bafilomycin A1 (Baf) induces an elevation of cytosolic Ca(2+) and acidification in neuronal cells via inhibition of the V-ATPase. Also, Baf uncouples mitochondria in differentiated PC12 ((d)PC12), (d)SH-SY5Y cells and cerebellar granule neurons, and markedly elevates their respiration. This respiratory response in (d)PC12 is accompanied by morphological changes in the mitochondria and decreases the mitochondrial pH, Ca(2+) and ΔΨm. The response to Baf is regulated by cytosolic Ca(2+) fluxes from the endoplasmic reticulum...
March 2011: Cellular and Molecular Life Sciences: CMLS
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