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Autophagy, apoptosis, lung cancer

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https://www.readbyqxmd.com/read/28209994/reversal-of-the-apoptotic-resistance-of-non-small-cell-lung-carcinoma-towards-trail-by-natural-product-toosendanin
#1
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
#2
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
#3
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/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
#4
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/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
#5
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/28151959/continuous-treatment-with-fts-confers-resistance-to-apoptosis-and-affects-autophagy
#6
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/28119810/asiatic-acid-inhibits-lung-cancer-cell-growth-in-vitro-and-in-vivo-by-destroying-mitochondria
#7
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
https://www.readbyqxmd.com/read/28039459/a-novel-glutaminase-inhibitor-968-inhibits-the-migration-and-proliferation-of-non-small-cell-lung-cancer-cells-by-targeting-egfr-erk-signaling-pathway
#8
Tianyu Han, Meng Guo, Tingting Zhang, Mingxi Gan, Caifeng Xie, Jian-Bin Wang
Metabolic reprogramming is critical for cancer cell proliferation. Glutaminolysis which provides cancer cells with bioenergetics and intermediates for macromolecular synthesis have been intensively studied in recent years. Glutaminase C (GAC) is the first and rate-limiting enzyme in glutaminolysis and plays important roles in cancer initiation and progression. We previously screened a small molecule named 968, a specific inhibitor of GAC, to block the proliferation of human breast cancer cells. In this study, we found that 968 effectively inhibited NSCLC cell proliferation and migration and arrested G0/G1 phase of cell cycle...
December 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/28035061/cordycepin-induces-autophagy-mediated-c-flipl-degradation-and-leads-to-apoptosis-in-human-non-small-cell-lung-cancer-cells
#9
Xinghui Yu, Jianya Ling, Xianfang Liu, Sen Guo, Yidan Lin, Xiangguo Liu, Ling Su
Cordycepin, a main active composition extracted from Cordyceps militaris, has been reported to exert anti-tumor activity in a broad spectrum of cancer types. However, the function of cordycepin on human non-small cell lung cancer cells is still obscure. Our present work showed that cordycepin inhibited cell growth by inducing apoptosis and autophagy in human NSCLC cells. Further study revealed that cordycepin triggered extrinsic apoptosis associated with down-regulation of c-FLIPL which suppresses the activity of caspase-8...
January 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/27939888/chaperone-mediated-autophagy-promotes-lung-cancer-cell-survival-through-selective-stabilization-of-the-pro-survival-protein-mcl1
#10
Junya Suzuki, Wataru Nakajima, Hidenori Suzuki, Yumi Asano, Nobuyuki Tanaka
Autophagy is a dynamic recycling system using lysosomal proteolysis that produces new proteins and energy for cellular renovation and homeostasis. Although macroautophagy is known to serve as a survival pathway in many cancer cells, the role of chaperone-mediated autophagy (CMA), a selective protein degradation system, in cancer is not fully understood. Here, we demonstrated that lysosomal proteolysis, but not macroautophagy, attenuated apoptosis induced by the tyrosine kinase inhibitor, crizotinib, in the non-small-cell lung cancer (NSCLC) cell line, EBC1...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27935858/paradoxical-induction-of-growth-arrest-and-apoptosis-by-egf-via-the-up-regulation-of-pten-by-activating-redox-factor-1-egr-1-in-human-lung-cancer-cells
#11
Je-Won Ryu, Sung Sik Choe, Seung-Hee Ryu, Eun-Young Park, Byoung Wook Lee, Tae Keun Kim, Chang Hoon Ha, Sang-Wook Lee
Epidermal growth factor (EGF) signaling promotes cell proliferation and survival in several types of cancer. Here, however, we showed that EGF inhibits proliferation and promotes programmed cell death in non-small cell lung cancer (NSCLC) cells. In A549 cells, EGF increased redox factor-1 (Ref-1) expression and the association of Ref-1 with zinc finger-containing transcriptional regulator (EGR1) via activation of p22phox, RAC1, and an NADPH oxidase subunit. EGF increased p22phox and RAC1 expression through activation of purinergic receptors (P2Y)...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27914529/agglutinin-isolated-from-arisema-heterophyllum-blume-induces-apoptosis-and-autophagy-in-a549-cells-through-inhibiting-pi3k-akt-pathway-and-inducing-er-stress
#12
Li-Xing Feng, Peng Sun, Tian Mi, Miao Liu, Wang Liu, Si Yao, Yi-Min Cao, Xiao-Lu Yu, Wan-Ying Wu, Bao-Hong Jiang, Min Yang, De-An Guo, Xuan Liu
Arisaema heterophyllum Blume is one of the three medicinal plants known as traditional Chinese medicine Rhizoma Arisaematis (RA). RA has been popularly used to treat patients with convulsions, inflammation, and cancer for a long time. However, the underlying mechanisms for RA effects are still unclear. The present study was designed to determine the cytotoxicity of agglutinin isolated from Arisema heterophyllum Blume (AHA) and explore the possible mechanisms in human non-small-cell lung cancer A549 cells. AHA with purity up to 95% was isolated and purified from Arisaema heterophyllum Blume using hydrophobic interaction chromatography...
November 2016: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/27890727/synthetic-tambjamine-analogues-induce-mitochondrial-swelling-and-lysosomal-dysfunction-leading-to-autophagy-blockade-and-necrotic-cell-death-in-lung-cancer
#13
Ananda M Rodilla, Luís Korrodi-Gregório, Elsa Hernando, Pilar Manuel-Manresa, Roberto Quesada, Ricardo Pérez-Tomás, Vanessa Soto-Cerrato
Current pharmacological treatments for lung cancer show very poor clinical outcomes, therefore, the development of novel anticancer agents with innovative mechanisms of action is urgently needed. Cancer cells have a reversed pH gradient compared to normal cells, which favours cancer progression by promoting proliferation, metabolic adaptation and evasion of apoptosis. In this regard, the use of ionophores to modulate intracellular pH appears as a promising new therapeutic strategy. Indeed, there is a growing body of evidence supporting ionophores as novel antitumour drugs...
February 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27886851/the-role-of-necroptosis-in-pulmonary-diseases
#14
REVIEW
Kenji Mizumura, Shuichiro Maruoka, Yasuhiro Gon, Augustine M K Choi, Shu Hashimoto
By regulating the cell number and eliminating harmful cells, programmed cell death plays a critical role in development, homeostasis, and disease. While apoptosis is a recognized form of programmed cell death, necrosis was considered a type of uncontrolled cell death induced by extreme physical or chemical stress. However, recent studies have revealed the existence of a genetically programmed and regulated form of necrosis, termed necroptosis. Necroptosis is defined as necrotic cell death that is dependent on receptor-interacting protein kinase 3 (RIPK3)...
November 2016: Respiratory Investigation
https://www.readbyqxmd.com/read/27814589/er-chaperone-grp78-regulates-autophagy-by-modulation-of-p53-localization
#15
Mohd Kamil, Ejazul Haque, Safia Irfan, Saba Sheikh, Adria Hasan, Aamir Nazir, Mohtashim Lohani, Snober S Mir
GRP78 (glucose regulated protein 78) is a major Endoplasmic Reticulum (ER) chaperone that plays a pivotal role in normal ER functioning. Its increased expression also works as an indicator of ER stress. Its anti-apoptotic and pro-autophagic activity makes it an intriguing target to study the relationship between GRP78 and p53, which is also a major regulator of apoptosis and autophagy. Here, we studied the effect of Rotenone and Parathion on human lung cancer cells (A549 cell line) specifically with respect to ER stress and its association with different cell death pathways...
January 1, 2017: Frontiers in Bioscience (Elite Edition)
https://www.readbyqxmd.com/read/27811372/the-induction-of-autophagy-against-mitochondria-mediated-apoptosis-in-lung-cancer-cells-by-a-ruthenium-ii-imidazole-complex
#16
Lanmei Chen, Guodong Li, Fa Peng, Xinming Jie, Guangzhi Dongye, Kangrong Cai, Ruibing Feng, Baojun Li, Qingwang Zeng, Kaiyi Lun, Jincan Chen, Bilian Xu
In the present study, it was found that the ruthenium (II) imidazole complex [Ru(Im)4(dppz)]2+ (Ru1) could induce significant growth inhibition and apoptosis in A549 and NCI-H460 cells. Apart from the induction of apoptosis, it was reported for the first time that Ru1 induced an autophagic response in A549 and NCI-H460 cells as evidenced by the formation of autophagosomes, acidic vesicular organelles (AVOs), and the up-regulation of LC3-II. Furthermore, scavenging of reactive oxygen species (ROS) by antioxidant NAC or Tiron inhibited the release of cytochrome c, caspase-3 activity, and eventually rescued cancer cells from Ru1-mediated apoptosis, suggesting that Ru1 inducing apoptosis was partially caspase 3-dependent by triggering ROS-mediated mitochondrial dysfunction in A549 and NCI-H460 cells...
November 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27765907/activation-of-endoplasmic-reticulum-stress-promotes-autophagy-and-apoptosis-and-reverses-chemoresistance-of-human-small-cell-lung-cancer-cells-by-inhibiting-the-pi3k-akt-mtor-signaling-pathway
#17
Xin-Shuang Yu, Juan Du, Yu-Jun Fan, Feng-Jun Liu, Li-Li Cao, Ning Liang, De-Guo Xu, Jian-Dong Zhang
OBJECTIVE: This study aims to investigate the effects of endoplasmic reticulum stress (ERS) on autophagy, apoptosis and chemoresistance of human small cell lung cancer (SCLC) cells via the PI3K/AKT/mTOR signaling pathway. RESULTS: The expressions of ERS-related proteins (PEAK, eIF2α and CHOP) up-regulated, autophagy-related proteins (LC3, LC3-II and Beclin1) and apoptosis-related proteins (Bax and procaspase-3) down-regulated in NCI-H446 and H69 cells after tunicamycin treatment for 24 h...
October 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27713168/the-aurora-kinase-a-inhibitor-tc-a2317-disrupts-mitotic-progression-and-inhibits-cancer-cell-proliferation
#18
Yoo Hong Min, Wootae Kim, Ja-Eun Kim
Mitotic progression is crucial for the maintenance of chromosomal stability. A proper progression is ensured by the activities of multiple kinases. One of these enzymes, the serine/threonine kinase Aurora A, is required for proper mitosis through the regulation of centrosome and spindle assembly. In this study, we functionally characterized a newly developed Aurora kinase A inhibitor, TC-A2317. In human lung cancer cells, TC-A2317 slowed proliferation by causing aberrant formation of centrosome and microtubule spindles and prolonging the duration of mitosis...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27697723/anticancer-effect-of-szc015-on-lung-cancer-cells-through-ros-dependent-apoptosis-and-autophagy-induction-mechanisms-in-vitro
#19
Bin Sun, Lei Gao, Anil Ahsan, Peng Chu, Yanlin Song, Hailong Li, Zonghui Zhang, Yuan Lin, Jinyong Peng, Zhicheng Song, Shisheng Wang, Zeyao Tang
Oleanolic acid (OA) and its several derivatives possess various pharmacological activities, such as antitumor and anti-inflammation. In present study, anticancer effect of SZC015, an OA derivative, and its underlying mechanisms were investigated. We demonstrated that cell viability was significantly decreased in SZC015-treated lung cancer cells, but has less cytotoxicity in human bronchial epithelial cell line. Further investigation verified that apoptosis and autophagy induction and G0/G1 phase arrest were observed in SZC015-treated H322 cells...
November 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27692344/autophagy-inhibition-upregulates-cd4-tumor-infiltrating-lymphocyte-expression-via-mir-155-regulation-and-trail-activation
#20
Paul Zarogoulidis, Savvas Petanidis, Kalliopi Domvri, Efrosini Kioseoglou, Doxakis Anestakis, Lutz Freitag, Konstantinos Zarogoulidis, Wolfgang Hohenforst-Schmidt, Wilfried Eberhardt
Chemoresistance is a major challenge in lung cancer treatment. Recent findings have revealed that autophagic mechanism contributes significantly to immunosuppressive related chemoresistance. For that reason, targeting autophagy-related immunosuppression is an important approach to reverse tumor drug resistance. In this study, we report for the first time that autophagy inhibition triggers upregulation of CD4(+), Foxp3(+) tumor infiltrating lymphocytes in late metastatic lung cancer tissues. Furthermore, autophagy blockage induces chemosensitization to carboplatin, immune activation and cell cycle arrest...
December 2016: Molecular Oncology
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