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https://www.readbyqxmd.com/read/28223119/neferine-augments-therapeutic-efficacy-of-cisplatin-through-ros-mediated-non-canonical-autophagy-in-human-lung-adenocarcinoma-a549%C3%A2-cells
#1
Sivalingam Kalai Selvi, Amirthalingam Vinoth, Thiyagarajan Varadharajan, Ching Feng Weng, Viswanadha Vijaya Padma
Combination of dietary components with chemotherapy drugs is an emerging new strategy for cancer therapy to increase antitumor responses. Neferine, major bisbenzylisoquinoline alkaloid isolated from the seed embryo of Nelumbo nucifera (Lotus). In the present study, we investigated the efficacy of the combinatorial regimen of neferine and cisplatin compared to cisplatin high dose in human lung adenocarcinoma (A549) cells. Co-treatment with neferine enhanced cisplatin-induced autophagy in A549 cells was accompanied by Acidic vesicular accumulation (AVO), enhanced generation of reactive oxygen species (ROS) and depletion of intracellular glutathione (GSH), down regulation of PI3K/AKT/mTOR pathway, conversion of LC3B-I to LC3B-II...
February 18, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28217691/%C3%AE-1-antitrypsin-deficiency-a-misfolded-secretory-protein-variant-with-unique-effects-on-the-endoplasmic-reticulum
#2
David H Perlmutter
In the classical form of α1-antitrypsin deficiency (ATD) a point mutation leads to accumulation of a misfolded secretory glycoprotein in the endoplasmic reticulum (ER) of liver cells and so ATD has come to be considered a prototypical ER storage disease. It is associated with two major types of clinical disorders, chronic obstructive pulmonary disease (COPD) by loss-of-function mechanisms and hepatic cirrhosis and carcinogenesis by gain-of-function mechanisms. The lung disease predominantly results from proteolytic damage to the pulmonary connective tissue matrix because of reduced levels of protease inhibitor activity of α1-anitrypsin (AT) in the circulating blood and body fluids...
September 2016: Endoplasmic Reticulum Stress in Diseases
https://www.readbyqxmd.com/read/28214844/autophagy-activation-by-rapamycin-before-hypoxia-reoxygenation-reduces-endoplasmic-reticulum-stress-in-alveolar-epithelial-cells
#3
Tao Fan, Lei Chen, Zhixin Huang, Wei Wang, Boyou Zhang, Yao Xu, Zhangfan Mao, Hao Hu, Qing Geng
BACKGROUND: To determine potential effects of autophagy activation on hypoxia-reoxygenation (H/R) induced damage of a rat alveolar epithelial cell line. METHODS: CCL149 cells were subjected to autophagy agonist (rapamycin, Rap), autophagy inhibitor (3-methyladenine, 3-MA) or PBS for 1 h before H/R treatment for 2 h, 4 h and 6 h. The optimal concentration of Rap (150 nM, 200 nM and 250 nM) or 3-MA (5 mM, 10 mM and 15 mM) was obtained from MTT assay. Autophagy was determined by fluorescence microscopy of eRFP-LC3 positive cells, transmission electron microscopy of autophagosome, western blot of LC3, AMPK, Beclin-1, HDAC6 and p62 proteins...
January 17, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28212561/the-tlr7-agonist-imiquimod-induces-anti-cancer-effects-via-autophagic-cell-death-and-enhances-anti-tumoral-and-systemic-immunity-during-radiotherapy-for-melanoma
#4
Jeong Hyun Cho, Hyo-Ji Lee, Hyun-Jeong Ko, Byung-Il Yoon, Jongseon Choe, Keun-Cheol Kim, Tae-Wook Hahn, Jeong A Han, Sun Shim Choi, Young Mee Jung, Kee-Ho Lee, Yun-Sil Lee, Yu-Jin Jung
Toll-like receptor (TLR) ligands are strongly considered immune-adjuvants for cancer immunotherapy and have been shown to exert direct anti-cancer effects. This study was performed to evaluate the synergistic anti-cancer and anti-metastatic effects of the TLR7 agonist imiquimod (IMQ) during radiotherapy for melanoma. The pretreatment of B16F10 or B16F1 cells with IMQ combined with γ-ionizing radiation (IR) led to enhanced cell death via autophagy, as demonstrated by increased expression levels of autophagy-related genes, and an increased number of autophagosomes in both cell lines...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28209994/reversal-of-the-apoptotic-resistance-of-non-small-cell-lung-carcinoma-towards-trail-by-natural-product-toosendanin
#5
Xin Li, Ming You, Yong-Jian Liu, Lin Ma, Pei-Pei Jin, Ri Zhou, Zhao-Xin Zhang, Baojin Hua, Xiao-Jun Ji, Xiao-Ying Cheng, Fangzhou Yin, Yan Chen, Wu Yin
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively triggers cancer cell death via its association with death receptors on the cell membrane, but exerts negligible side effects on normal cells. However, some non-small-cell lung carcinoma (NSCLC) patients exhibited resistance to TRAIL treatment in clinical trials, and the mechanism varies. In this study, we described for the first time that toosendanin (TSN), a triterpenoid derivative used in Chinese medicine for pain management, could significantly sensitize human primary NSCLC cells or NSCLC cell lines to TRAIL-mediated apoptosis both in vitro and in vivo, while showing low toxicity against human primary cells or tissues...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209717/autophagy-metabolism-and-cancer
#6
Jessie Yanxiang Guo, Eileen White
Macroautophagy (autophagy hereafter) is a process that collects cytoplasmic components, particularly mitochondria, and degrades them in lysosomes. In mammalian systems, basal autophagy levels are normally low but are profoundly stimulated by starvation and essential for survival. Cancer cells up-regulate autophagy and can be more autophagy-dependent than most normal tissues. Genetic deficiency in essential autophagy genes in tumors in many autochthonous mouse models for cancer reduces tumor growth. In K-ras(G12D)-driven non-small cell lung cancer (NSCLC) and other models, autophagy sustains metabolism and survival...
February 16, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28208579/role-of-autophagy-and-apoptosis-in-non-small-cell-lung-cancer
#7
REVIEW
Guangbo Liu, Fen Pei, Fengqing Yang, Lingxiao Li, Amit Dipak Amin, Songnian Liu, J Ross Buchan, William C Cho
Non-small-cell lung cancer (NSCLC) constitutes 85% of all lung cancers, and is the leading cause of cancer-related death worldwide. The poor prognosis and resistance to both radiation and chemotherapy warrant further investigation into the molecular mechanisms of NSCLC and the development of new, more efficacious therapeutics. The processes of autophagy and apoptosis, which induce degradation of proteins and organelles or cell death upon cellular stress, are crucial in the pathophysiology of NSCLC. The close interplay between autophagy and apoptosis through shared signaling pathways complicates our understanding of how NSCLC pathophysiology is regulated...
February 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28202616/dna-repair-interacts-with-autophagy-to-regulate-inflammatory-responses-to-pulmonary-hyperoxia
#8
Yan Ye, Ping Lin, Weidong Zhang, Shirui Tan, Xikun Zhou, Rongpeng Li, Qinqin Pu, Jonathan L Koff, Archana Dhasarathy, Feng Ma, Xin Deng, Jianxin Jiang, Min Wu
Oxygen is supplied as a supportive treatment for patients suffering from acute respiratory distress syndrome. Unfortunately, high oxygen concentration increases reactive oxygen species generation, which causes DNA damage and ultimately cell death in the lung. Although 8-oxoguanine-DNA glycosylase (OGG-1) is involved in repairing hyperoxia-mediated DNA damage, the underlying molecular mechanism remains elusive. In this study, we report that ogg-1-deficient mice exhibited a significant increase of proinflammatory cytokines (TNF-α, IL-6, and IFN-γ) in the lung after being exposed to 95% oxygen...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28195146/the-inhibition-of-lung-cancer-cell-migration-by-ahr-regulated-autophagy
#9
Chi-Hao Tsai, Ching-Hao Li, Yu-Wen Cheng, Chen-Chen Lee, Po-Lin Liao, Cheng-Hui Lin, Shih-Hsuan Huang, Jaw-Jou Kang
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is highly expressed in multiple organs and tissues. Whereas AhR mediates the metabolism of xenobiotic and endogenous compounds, its novel function in cancer epithelial-mesenchymal transition (EMT) remains controversial. Autophagy also participates in tumour progression through its functions in cell homeostasis and facilitates adaptation to EMT progression. In the present study, we found that AhR-regulated autophagy positively modulates EMT in non-small cell lung cancer cells...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28192114/sirolimus-and-autophagy-inhibition-in-lam-results-of-a-phase-i-clinical-trial
#10
Souheil El-Chemaly, Angelo Taveira-Dasilva, Hilary J Goldberg, Elizabeth Peters, Mary Haughey, Don Bienfang, Amanda M Jones, Patricia Julien-Williams, Ye Cui, Julian A Villalba, Shefali Bagwe, Rie Maurer, Ivan O Rosas, Joel Moss, Elizabeth P Henske
BACKGROUND: Animal and cellular studies support the importance of autophagy inhibition in lymphangioleiomyomatosis (LAM). In a cohort of subjects with LAM, we tested the hypothesis that treatment with sirolimus and hydroxycholoroquine (an autophagy inhibitor) at 2 different dose levels is safe and well tolerated. Secondary endpoints included changes in lung function. METHODS: This 48-week, two-center Phase I trial evaluated the safety of escalating oral hydroxychloroquine doses (100-200 mg) given twice a day in combination with sirolimus to eligible patients ≥18 years old with LAM...
February 10, 2017: Chest
https://www.readbyqxmd.com/read/28158287/the-apoptotic-effect-of-1-s-1-acetoxychavicol-acetate-aca-enhanced-by-inhibition-of-non-canonical-autophagy-in-human-non-small-cell-lung-cancer-cells
#11
Sophia P M Sok, Norhafiza M Arshad, Mohamad Nurul Azmi, Khalijah Awang, Bulent Ozpolat, Noor Hasima Nagoor
Autophagy plays a role in deciding the fate of cells by inducing either survival or death. 1'S-1-acetoxychavicol acetate (ACA) is a phenylpropanoid isolated from rhizomes of Alpinia conchigera and has been reported previously on its apoptotic effects on various cancers. However, the effect of ACA on autophagy remains ambiguous. The aims of this study were to investigate the autophagy-inducing ability of ACA in human non-small cell lung cancer (NSCLC), and to determine its role as pro-survival or pro-death mechanism...
2017: PloS One
https://www.readbyqxmd.com/read/28157209/autophagy-induced-by-damps-facilitates-the-inflammation-response-in-lungs-undergoing-ischemia-reperfusion-injury-through-promoting-traf6-ubiquitination
#12
Xingguang Liu, Hao Cao, Jian Li, Bo Wang, Peng Zhang, Xu Dong Zhang, Zhongmin Liu, Hongbin Yuan, Zhenzhen Zhan
Lung ischemia-reperfusion (I/R) injury remains one of the most common complications after various cardiopulmonary surgeries. The inflammation response triggered by the released damage-associated molecular patterns (DAMPs) aggravates lung tissue damage. However, little is known about the role of autophagy in the pathogenesis of lung I/R injury. Here, we report that a variety of inflammation-related and autophagy-associated genes are rapidly upregulated, which facilitate the inflammation response in a minipig lung I/R injury model...
February 3, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28154825/bu-zhong-yi-qi-decoction-the-water-extract-of-chinese-traditional-herbal-medicine-enhances-cisplatin-cytotoxicity-in-a549-ddp-cells-through-induction-of-apoptosis-and-autophagy
#13
Ning Yu, Ying Xiong, Chun Wang
Cisplatin is one of the most active cytotoxic agents for non-small cell lung cancer (NSCLC) treatment. However, the development of cisplatin resistance is common. Bu-Zhong-Yi-Qi decoction (BZYQD), a Chinese traditional herbal medicine, is widely used for the enhancement of antitumor effect in other medications. In this study, we evaluated the effect and drug-resistance reversal mechanism of BZYQD combined with cisplatin on cisplatin-resistant A549/DDP cells. Our results showed that BZYQD exhibited direct cytotoxic and chemosensitizing effects...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28154798/activity-based-proteomics-reveals-heterogeneous-kinome-and-atp-binding-proteome-responses-to-mek-inhibition-in-kras-mutant-lung-cancer
#14
Jae-Young Kim, Paul A Stewart, Adam L Borne, Bin Fang, Eric A Welsh, Yian Ann Chen, Steven A Eschrich, John M Koomen, Eric B Haura
One way cancer cells can escape from targeted agents is through their ability to evade drug effects by rapidly rewiring signaling networks. Many protein classes, such as kinases and metabolic enzymes, are regulated by ATP binding and hydrolysis. We hypothesized that a system-level profiling of drug-induced alterations in ATP-binding proteomes could offer novel insights into adaptive responses. Here, we mapped global ATP-binding proteomes perturbed by two clinical MEK inhibitors, AZD6244 and MEK162, in KRAS mutant lung cancer cells as a model system harnessing a desthiobiotin-ATP probe coupled with LC-MS/MS...
June 2016: Proteomes
https://www.readbyqxmd.com/read/28151959/continuous-treatment-with-fts-confers-resistance-to-apoptosis-and-affects-autophagy
#15
Eran Schmukler, Eya Wolfson, Zvulun Elazar, Yoel Kloog, Ronit Pinkas-Kramarski
High percentage of human cancers involves alteration or mutation in Ras proteins, including the most aggressive malignancies, such as lung, colon and pancreatic cancers. FTS (Salirasib) is a farnesylcysteine mimetic, which acts as a functional Ras inhibitor, and was shown to exert anti-tumorigenic effects in vitro and in vivo. Previously, we have demonstrated that short-term treatment with FTS also induces protective autophagy in several cancer cell lines. Drug resistance is frequently observed in cancer cells exposed to prolonged treatment, and is considered a major cause for therapy inefficiency...
2017: PloS One
https://www.readbyqxmd.com/read/28150141/role-of-second-hand-smoke-shs-induced-proteostasis-autophagy-impairment-in-pediatric-lung-diseases
#16
Neel Patel, Christopher D Trumph, Manish Bodas, Neeraj Vij
BACKGROUND: Exposure to second-hand tobacco smoke (SHS) is one of the prime risk factors for chronic lung disease development. Smoking during pregnancy may lead to birth defects in the newborn that include pulmonary dysfunction, increased susceptibility to opportunistic pathogens, or initiation of childhood respiratory manifestations such as bronchopulmonary dysplasia (BPD). Moreover, exposure to SHS in early childhood can have negative impact on lung health, although the exact mechanisms are unclear...
December 2017: Molecular and Cellular Pediatrics
https://www.readbyqxmd.com/read/28147244/the-pi3k-inhibitor-gdc-0941-enhances-radiosensitization-and-reduces-chemoresistance-to-temozolomide-in-gbm-cell-lines
#17
Fei Shi, Hongchuan Guo, Rong Zhang, Hongyu Liu, Liangliang Wu, Qiyan Wu, Jialin Liu, Tianyi Liu, Qiuhang Zhang
Glioblastoma multiforme (GBM) is among the most lethal of all human tumors. It is the most frequently occurring malignant primary brain tumor in adults. The current standard of care (SOC) for GBM is initial surgical resection followed by treatment with a combination of temozolomide (TMZ) and ionizing radiation (IR). However, GBM has a dismal prognosis, and survivors have compromised quality of life owing to the adverse effects of radiation. GBM is characterized by overt activity of the phosphoinositide 3-kinase (PI3K) signaling pathway...
January 29, 2017: Neuroscience
https://www.readbyqxmd.com/read/28145905/mitochondria-in-the-spotlight-of-aging-and-idiopathic-pulmonary-fibrosis
#18
REVIEW
Ana L Mora, Marta Bueno, Mauricio Rojas
Idiopathic pulmonary fibrosis (IPF) is a chronic age-related lung disease with high mortality that is characterized by abnormal scarring of the lung parenchyma. There has been a recent attempt to define the age-associated changes predisposing individuals to develop IPF. Age-related perturbations that are increasingly found in epithelial cells and fibroblasts from IPF lungs compared with age-matched cells from normal lungs include defective autophagy, telomere attrition, altered proteostasis, and cell senescence...
February 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28125526/mir-155-alleviates-septic-lung-injury-by-inducing-autophagy-via-inhibition-of-transforming-growth-factor-%C3%AE-activated-binding-protein-2
#19
Fen Liu, Cheng Nie, Ning Zhao, Yan Wang, Yang Liu, Yong Li, Zhenguo Zeng, Chengzhi Ding, Qiang Shao, Cheng Qing, Liang Xia, Zhiyong Peng, Kejian Qian
BACKGROUND: The anti-inflammatory effect of miR-155 was closely linked to transforming growth factor-β-activated kinase-1-binding protein 2 (TAB2) and autophagy. This study investigated the role of miR-155 in attenuation of septic lung injury through TAB2 and autophagy in mouse model and in vitro. METHODS: Patients who underwent fiberoptic bronchoscope examination with or without septic lung injury were recruited for collection of bronchoalveolar lavage fluid (BALF) samples...
January 25, 2017: Shock
https://www.readbyqxmd.com/read/28119810/asiatic-acid-inhibits-lung-cancer-cell-growth-in-vitro-and-in-vivo-by-destroying-mitochondria
#20
Tiancong Wu, Ji Geng, Wenjie Guo, Jing Gao, Xixu Zhu
Asiatic acid (AA), a pentacyclic triterpene found in Centella asiatica, displays significant anti-proliferative effects on cancer cells in vitro although the underlying mechanism of this effect remains unknown. This study investigated the efficacy and mechanism of action of AA against lung cancer both in vivo and in vitro. Using the MTT assay, AA was found to induce apoptosis in a dose- and time-dependent manner, an effect enhanced by pretreatment with an autophagy inhibitor. It also elevated expression of microtubule-associated protein 1 light chain 3 (LC3) and decreased the expression of p62...
January 2017: Acta Pharmaceutica Sinica. B
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