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Autophagy, apoptosis, lung cancer

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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
#1
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...
November 24, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27886851/the-role-of-necroptosis-in-pulmonary-diseases
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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...
September 30, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27692344/autophagy-inhibition-upregulates-cd4-tumor-infiltrating-lymphocyte-expression-via-mir-155-regulation-and-trail-activation
#8
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...
September 16, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/27666552/-advances-in-the-research-of-autophagy-in-egfr-tki-treatment-and-resistance-%C3%A2-in-lung-cancer
#9
Qicheng Zhang, Ke Xu
Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is a group of targeted-drugs which effectively inhibits the growth of tumor cells with sensitive mutations in EGFR. However, the innate and acquired resistance are major obstacles of the efficiency. Autophagy is a highly conserved self-digesting process in cells, which is considered to be associated with cancer development andchemoresistance. The activation of EGFR may regulate autophagy through multiple signal pathways. EGFR-TKIs can induce autophagy, however, the function of the inducted autophagy remains biphasic...
September 20, 2016: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/27662422/anti-tumor-effects-of-cardiac-glycosides-on-human-lung-cancer-cells-and-lung-tumorspheres
#10
Vivek Kaushik, Juan Sebastian Yakisich, Neelam Azad, Yogesh Kulkarni, Rajkumar Venkatadri, Clayton Wright, Yon Rojanasakul, Anand Krishnan V Iyer
Lung cancer is a leading cause of cancer-related death in the United States. While several drugs have been developed that target individual biomarkers, their success has been limited due to intrinsic or acquired resistance for the specific targets of such drugs. A more effective approach is to target multiple pathways that dictate cancer progression. Cardiac glycosides demonstrate such multimodal effects on cancer cell survival, and our aim was to evaluate the effect of two naturally occurring monosaccaridic cardiac glycosides - Convallatoxin and Peruvoside on lung cancer cells...
September 23, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27660182/selective-anticancer-activity-of-the-novel-thiobenzanilide-63t-against-human-lung-adenocarcinoma-cells
#11
Malgorzata Kucinska, Hanna Piotrowska-Kempisty, Natalia Lisiak, Mariusz Kaczmarek, Hanna Dams-Kozlowska, Walter H Granig, Martina Höferl, Walter Jäger, Martin Zehl, Marek Murias, Thomas Erker
Previously, it has been reported that molecules built on the benzanilide and thiobenzanilide scaffold are the promising groups of compounds with several biological activities including antifungal, antimycotic, antibacterial, spasmolytic, and anticancer ones. In this study the mechanism of action of one selected thiobenzanilide derivative N,N'-(1,2-phenylene)bis3,4,5-trifluorobenzothioamide (63T) with strongest cytotoxic activity has been investigated for the first time in human lung adenocarcinoma (A549) and normal lung derived fibroblast (CCD39Lu) in a cell culture model...
December 2016: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/27639429/nrf2-but-not-autophagy-inhibition-is-associated-with-the-survival-of-wild-type-epidermal-growth-factor-receptor-non-small-cell-lung-cancer-cells
#12
Yan Zhou, Yuan Li, Hong-Min Ni, Wen-Xing Ding, Hua Zhong
Non-small cell lung cancer (NSCLC) is one of the most common malignancies in the world. Icotinib and Gefitinib are two epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) that have been used to treat NSCLC. While it is well known that mutations of EGFR can affect the sensitivity of NSCLC to the EGFR-TKI, other mechanisms may also be adopted by lung cancer cells to develop resistance to EGFR-TKI treatment. Cancer cells can use multiple adaptive mechanisms such as activation of autophagy and Nrf2 to protect against various stresses and chemotherapeutic drugs...
November 1, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27639426/inhibition-of-autophagy-by-andrographolide-resensitizes-cisplatin-resistant-non-small-cell-lung-carcinoma-cells-via-activation-of-the-akt-mtor-pathway
#13
Shanwei Mi, Gang Xiang, Daolu Yuwen, Jian Gao, Wenjie Guo, Xuefeng Wu, Xudong Wu, Yang Sun, Yongqian Su, Yan Shen, Qiang Xu
Resistance to cisplatin is a major obstacle for the success of non-small cell lung cancer therapy. The mechanisms underlying cisplatin resistance are not fully understood. In this study, we found that the increase of basal auotophagy accompanied the development of cisplatin resistance. Meanwhile the blockade of the Akt/mTOR pathway occurred in the process. Inhibition of this pathway was induced by cisplatin treatment in the resistant non-small cell lung carcinoma cells. Andrographolide, a natural diterpenoid, promoted the activation of the Akt/mTOR signaling by downregulating PTEN and suppressed autophagy, which subsequently resensitized the resistant cells to cisplatin-mediated apoptosis...
November 1, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27604425/gemcitabine-induced-autophagy-protects-human-lung-cancer-cells-from-apoptotic-death
#14
Hui-Mei Wu, Li-Jie Shao, Zi-Feng Jiang, Rong-Yu Liu
PURPOSE: Gemcitabine has been used as a therapeutic drug combined with cisplatin for the treatment of lung cancer patients. However, the prognosis is poor due to acquired resistance. Accumulating studies have revealed that autophagy may contribute to the drug resistance. Therefore, the present study is aimed to clarify the mechanisms underlying gemcitabine-acquired resistance. METHODS: SPC-A1 and A549 cells were incubated with gemcitabine followed by assessment of cell viability with MTT assays...
September 7, 2016: Lung
https://www.readbyqxmd.com/read/27602962/polyphyllin-g-induce-apoptosis-and-autophagy-in-human-nasopharyngeal-cancer-cells-by-modulation-of-akt-and-mitogen-activated-protein-kinase-pathways-in-vitro-and-in-vivo
#15
Jui-Chieh Chen, Ming-Ju Hsieh, Chih-Jung Chen, Jen-Tsun Lin, Yu-Sheng Lo, Yi-Ching Chuang, Su-Yu Chien, Mu-Kuan Chen
Polyphyllin G (also call polyphyllin VII), extract from rhizomes of Paris yunnanensis Franch, has been demonstrated to have strong anticancer activities in a wide variety of human cancer cell lines. Previous studies found that Polyphyllin G induced apoptotic cell death in human hepatoblastoma cancer and lung cancer cells. However, the underlying mechanisms of autophagy in human nasopharyngeal carcinoma (NPC) remain unclear. In this study, Polyphyllin G can potently induced apoptosis dependent on the activations of caspase-8, -3, and -9 and the changes of Bcl-2, Bcl-xL and Bax protein expression in different human NPC cell lines (HONE-1 and NPC-039)...
September 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27594089/the-roles-of-mir-25-and-its-targeted-genes-in-development-of-human-cancer
#16
Massimo Mallardo, Carmen Caiazza
MicroRNAs (miRNAs) are small noncoding RNAs able to suppress gene expression by targeting messenger RNAs for translational repression or, at lesser extent, degradation. miRNAs are widely expressed in tissues and organs and play fundamental roles in controlling cell proliferation, apoptosis, differentiation, cell migration, autophagy and metabolism. Uncontrolled expression of miRNAs has been associated with cancer progression, and miRNA up- or down-regulation has been linked to oncogenic and tumor-suppressive roles in cancers such as breast cancer, colorectal cancer, lung cancer, gastric cancer and glioblastoma...
September 4, 2016: MicroRNA
https://www.readbyqxmd.com/read/27580936/inhibition-of-caspase-9-aggravates-acute-liver-injury-through-suppression-of-cytoprotective-autophagy
#17
Rui Guo, Bin Lin, Jing Fei Pan, Emily C Liong, Ai Min Xu, Moussa Youdim, Man Lung Fung, Kwok Fai So, George L Tipoe
Acute liver disease is characterized by inflammation, oxidative stress and necrosis, which can greatly influence the long term clinical outcome and lead to liver failure or cancer. Here, we initially demonstrated the beneficial role of caspase-9-dependent autophagy in acute liver injury. Treatment with caspase-9 inhibitor z-LEHD-FMK in HepG2 cells, AML12 cells and C57BL/b6N mice exacerbated CCl4-induced acute hepatocellular damage, and also down-regulated autophagy markers expression levels, indicating that caspase-9 inhibition may aggravate acute liver damage by suppressing cytoprotective autophagy...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27572309/blockade-efficacy-of-mek-erk-dependent-autophagy-enhances-pi3k-akt-inhibitor-nvp-bkm120-s-therapeutic-effectiveness-in-lung-cancer-cells
#18
Hui Ren, Hua Guo, Asmitananda Thakur, Shuo Zhang, Ting Wang, Yiqian Liang, Puyu Shi, Lei Gao, Feng Liu, Jing Feng, Tianjun Chen, Tian Yang, Dong Shang, Johnson J Liu, Feng Xu, Mingwei Chen
NVP-BKM120 (BKM120) is a new pan-class I phosphatidylinositol-3 kinase (PI3K) inhibitor and has been tested in clinical trials as an anticancer agent. In this study, we determined whether BKM120 induces autophagy and the impact of autophagy induction on BKM120's growth-inhibitory activity. BKM120 potently induced elevation of autophagosome-bound type II LC3 (LC3-II) protein, predominantly in cell lines insensitive to BKM120, thereby inducing autophagy. The presence of lysosomal protease inhibitor chloroquine further enhanced the levels of LC3-II...
August 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27566579/-guaiol-regulates-rad51-stability-via-autophagy-to-induce-cell-apoptosis-in-non-small-cell-lung-cancer
#19
Qingyuan Yang, Jianchun Wu, Yingbin Luo, Nan Huang, Ni Zhen, Yun Zhou, Fenyong Sun, Zhi Li, Qiuhui Pan, Yan Li
(-)-Guaiol, generally known as an antibacterial compound, has been found in many medicinal plants. Its roles in tumor suppression are still under investigation. In the study, we mainly focused on exploring its applications in dealing with non-small cell lung cancer (NSCLC) and the underlying mechanisms. Here, we show that (-)-Guaiol significantly inhibits cell growth of NSCLC cells both in vitro and in vivo. Further high throughput analysis reveals that RAD51, a pivotal factor in homologous recombination repair, is a potential target for it...
August 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27565443/inhibition-of-autophagy-enhances-heat-induced-apoptosis-in-human-non-small-cell-lung-cancer-cells-through-er-stress-pathways
#20
REVIEW
Wen-Yue Xie, Xiang-Dong Zhou, Juan Yang, Ling-Xiu Chen, Dan-Hua Ran
The occurrence and mechanisms of autophagy induced by heat stress are not well known in lung cancer cells. Here, we have demonstrated that heat stress induces autophagy in A549 and NCI-H460 cells through morphological and biochemical analyses. The inhibition of autophagy by chloroquine, 3-methyladenine and Beclin 1 siRNA enhanced heat-induced apoptosis. Moreover, the combination of chloroquine and heat stress inhibited tumor growth and enhanced apoptosis in vivo experiments. In addition, heat-induced autophagy involved the ER stress pathway (PERK- or IRE1-dependent)...
October 1, 2016: Archives of Biochemistry and Biophysics
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