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Lc3-1, autophagy,apoptosis, lung

Tao Fan, Lei Chen, Zhixin Huang, Zhangfan Mao, Wei Wang, Boyou Zhang, Yao Xu, Shize Pan, Hao Hu, Qing Geng
To study the impact of autophagy on alveolar macrophage apoptosis and its mechanism in the early stages of hypoxia, we established a cell hypoxia-reoxygenation model and orthotopic left lung ischemia-reperfusion model. Rat alveolar macrophages stably expressing RFP-LC3 were treated with autophagy inhibitor (3-methyladenine, 3-MA) or autophagy promoter (rapamycin), followed by hypoxia-reoxygenation treatment 2 h, 4 h or 6 h later. Twenty Sprague-Dawley male rats were randomly divided into four different groups: no blocking of left lung hilum (model group), left lung hilum blocked for 1h with DMSO lavage (control group), left lung hilum blocked for 1 h with 100 ml/kg 3-MA (5 μmol/L) lavage (3-MA group), and left lung hilum blocked for 1 h with 100 ml/kg rapamycin (250 nmol/L) lavage (rapamycin group)...
November 24, 2016: Oncotarget
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
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
Li Lin, Lijun Zhang, Liangzhu Yu, Lu Han, Wanli Ji, Hui Shen, Zhenwu Hu
OBJECTIVES: Abnormal lung cell death including autophagy and apoptosis is the central feature in acute lung injury (ALI). To identify the cellular mechanisms and the chronology by which different types of lung cell death are activated during lipopolysaccharide (LPS)-induced ALI, we decided to evaluate autophagy (by LC3-II and autophagosome) and apoptosis (by caspase-3) at different time points after LPS treatment in a rat model of LPS-induced ALI. MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into two groups: control group and LPS group...
June 2016: Iranian Journal of Basic Medical Sciences
Martin Gengenbacher, Natalie Nieuwenhuizen, Alexis Vogelzang, Haipeng Liu, Peggy Kaiser, Stefanie Schuerer, Doris Lazar, Ina Wagner, Hans-Joachim Mollenkopf, Stefan H E Kaufmann
UNLABELLED: The current tuberculosis (TB) vaccine, Mycobacterium bovis Bacillus Calmette-Guérin (BCG), provides insufficient protection against pulmonary TB. Previously, we generated a listeriolysin-expressing recombinant BCG strain, which to date has successfully completed phase I and phase IIa clinical trials. In an attempt to further improve efficacy, we deleted the antiapoptotic virulence gene nuoG, encoding NADH dehydrogenase 1 subunit G, from BCG ΔureC::hly In vitro, deletion of nuoG unexpectedly led to strongly increased recruitment of the autophagosome marker LC3 to the engulfed vaccine, suggesting that nuoG also affects xenophagic pathways...
May 24, 2016: MBio
Noor Shahirah Suparji, Gomathi Chan, Hani Sapili, Norhafiza M Arshad, Lionel L A In, Khalijah Awang, Noor Hasima Nagoor
Geranylated 4-phenylcoumarins, DMDP-1 & -2 isolated from Mesua elegans were investigated for anticancer potential against human prostate cancer cells. Treatment with DMDP-1 & -2 resulted in cell death in a time and dose dependent manner in an MTT assay on all cancer cell lines tested with the exception of lung adenocarcinoma cells. DMDP-1 showed highest cytotoxic efficacy in PC-3 cells while DMDP-2 was most potent in DU 145 cells. Flow cytometry indicated that both coumarins were successful to induce programmed cell death after 24 h treatment...
2016: PloS One
Ting Fu, Ling Wang, Xiang-nan Jin, Hai-juan Sui, Zhou Liu, Ying Jin
AIM: Hyperoside (quercetin-3-O-β-D-galactopyranoside) is a flavonol glycoside found in plants of the genera Hypericum and Crataegus, which exhibits anticancer, anti-oxidant, and anti-inflammatory activities. In this study we investigated whether autophagy was involved in the anticancer mechanisms of hyperoside in human non-small cell lung cancer cells in vitro. METHODS: Human non-small cell lung cancer cell line A549 was tested, and human bronchial epithelial cell line BEAS-2B was used for comparison...
April 2016: Acta Pharmacologica Sinica
Zhenzhong Su, Ke Wang, Ranwei Li, Jinzhi Yin, Yuqiu Hao, Xuejiao Lv, Junyao Li, Lijing Zhao, Yanwei Du, Ping Li, Jie Zhang
BACKGROUND: Dysfunctions in autophagy and apoptosis are closely interacted and play an important role in cancer development. RNA binding motif 5 (RBM5) is a tumor suppressor gene, which inhibits tumor cells' growth and enhances chemosensitivity through inducing apoptosis in our previous studies. In this study, we investigated the relationship between RBM5 overexpression and autophagy in human lung adenocarcinoma cells. METHODS: Human lung adenocarcinoma cancer (A549) cells were cultured in vitro and were transiently transfected with a RBM5 expressing plasmid (GV287-RBM5) or plasmid with scrambled control sequence...
February 29, 2016: World Journal of Surgical Oncology
Jae-Kyo Jeong, Sangiliyandi Gurunathan, Min-Hee Kang, Jae Woong Han, Joydeep Das, Yun-Jung Choi, Deug-Nam Kwon, Ssang-Goo Cho, Chankyu Park, Han Geuk Seo, Hyuk Song, Jin-Hoi Kim
Solid tumors are frequently associated with resistance to chemotherapy because the fraction of hypoxic tumor cells is substantial. To understand the underlying mechanism of hypoxia on silver nanoparticle (AgNPs)-induced apoptosis, the expression of hypoxia-inducible factor (HIF)-1α, a hallmark of hypoxia, was measured in the presence and absence of AgNPs. The results showed that HIF-1α expression was upregulated after AgNPs treatment under both hypoxic and normoxic conditions. Cell viability assays showed that AgNPs promoted cell death in cancer cells but not in non-cancer cells, as cancer cells are slightly more acidic than normal cells...
February 12, 2016: Scientific Reports
You-Zhi Xu, Yong-Huai Li, Wen-Jie Lu, Kun Lu, Chun-Ting Wang, Yan Li, Hong-Jun Lin, Li-Xin Kan, Sheng-Yong Yang, Si-Ying Wang, Ying-Lan Zhao
Cancer cells activate autophagy in response to anticancer therapies. Autophagy induction is a promising therapeutic approach to treat cancer. In a previous study, YL4073 inhibited the growth of liver cancer and induced liver cancer cell apoptosis. Here, we demonstrated the anticancer activity and specific mechanisms of YL4073 in Lewis lung carcinoma LL/2 cells. Our results show that YL4073-induced autophagy was followed by apoptotic cell death. The anticancer and autophagy stimulating efficacy was confirmed by several factors, including the appearance of autophagic vacuoles, formation of acidic vesicular organelles, recruitment of microtubule-associated protein 1 light chain 3 II (LC3-II) to the autophagosomes, conversion and cleavage of LC3-I to LC3-II, upregulation of Beclin 1 expression, and formation of the Atg12-Atg5 conjugate in LL/2 cells after YL4073 treatment for 24 or 48 h...
April 2016: Oncology Reports
Yogesh M Kulkarni, Vivek Kaushik, Neelam Azad, Clayton Wright, Yon Rojanasakul, George O'Doherty, Anand Krishnan V Iyer
We have synthesized a novel derivative of Digitoxin, termed "MonoD", which demonstrates cytotoxic effects in lung cancer cells with much higher potency as compared to Digitoxin. Our data show that within 1 h of MonoD treatment, H460 cells showed increased oxidative stress, increased formation of autophagic vacuoles, and increased expression of pro-autophagic markers Beclin-1 and LC3-II. Cells pretreated with MnTBAP, a superoxide scavenger not only lowered superoxide production, but also had lower levels of LC3-II and Beclin-1...
April 2016: Journal of Cellular Physiology
Clayton Wright, Anand Krishnan V Iyer, Yogesh Kulkarni, Neelam Azad
Autophagy is a catabolic cellular mechanism involving lysosomal degradation of unwanted cellular components. Interaction between Beclin-1 and Bcl-2 proteins is known to play a critical role in the initiation of autophagy. We report that malignantly transformed lung epithelial cells are resistant to autophagy and express lower basal levels of autophagic proteins, Beclin-1 and LC3-II as compared to non-tumorigenic cells. Additionally, increased levels of nitric oxide (NO) and Bcl-2 were observed in transformed cells...
February 2016: Journal of Cellular Biochemistry
Ruolin Zhao, Meijuan Chen, Zequn Jiang, Fengming Zhao, Beili Xi, Xu Zhang, Haian Fu, Kunfu Zhou
Platycodin-D (PD) is an effective triterpene saponin extracted from the root of Platycodon grandiflorum which has been used clinically to treat pulmonary diseases in traditional Chinese medicine. Recently, it has been reported that PD has anti-tumor effects in various cancer models through the induction of apoptosis. However, whether PD induces autophagy in both cell lines and its molecular mechanisms have not been elucidated. Here, our present study confirmed that PD induced autophagy in both NCI-H460 and A549 cells via up-regulating the expression levels of Atg-3, Atg-7 and Beclin-1...
2015: Journal of Cancer
Ruiguang Zhang, Yan Li, Zhongliang Wang, Lingjuan Chen, Xiaorong Dong, Xiu Nie
Non-small cell lung cancer is commonly seen with higher morbidity and mortality. High-mobility group protein 1 (HMGB1) is a highly conserved nuclear protein, which is involved in multiple human diseases including cancers. However, the mechanisms of HMGB1 in non-small cell lung cancer remain unclear. The goal of the present study is to identify the relationship between HMGB1 and the progresssion of non-small cell lung cancer and investigate the molecular mechanism of HMGB1 in non-small lung cancer cell lines...
November 2015: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Shu-Ting Pan, Zhi-Wei Zhou, Zhi-Xu He, Xueji Zhang, Tianxin Yang, Yin-Xue Yang, Dong Wang, Jia-Xuan Qiu, Shu-Feng Zhou
5,6-Dimethylxanthenone 4-acetic acid (DMXAA), also known as ASA404 and vadimezan, is a potent tumor blood vessel-disrupting agent and cytokine inducer used alone or in combination with other cytotoxic agents for the treatment of non-small cell lung cancer (NSCLC) and other cancers. However, the latest Phase III clinical trial has shown frustrating outcomes in the treatment of NSCLC, since the therapeutic targets and underlying mechanism for the anticancer effect of DMXAA are not yet fully understood. This study aimed to examine the proteomic response to DMXAA and unveil the global molecular targets and possible mechanisms for the anticancer effect of DMXAA in NSCLC A549 cells using a stable-isotope labeling by amino acids in cell culture (SILAC) approach...
2015: Drug Design, Development and Therapy
Jin Hong Xu, He Ping Yang, Xiang Dong Zhou, Hai Jing Wang, Liang Gong, Chun Lan Tang
OBJECTIVE: To investigate the effects of bisdemethoxycurcumin (BDMC) on non-small cell lung cancer (NSCLC) cell line, A549, and the highly metastatic lung cancer 95D cells. METHODS: CCK-8 assay was used to assess the effect of BDMC on cytotoxicity. Flow cytometry was used to evaluate apoptosis. Western blot analysis, electron microscopy, and quantification of GFP-LC3 punctuates were used to test the effect of BDMC on autophagy and apoptosis of lung cancer cells...
February 2015: Biomedical and Environmental Sciences: BES
Jianhong Yang, Yongzhao Zhou, Xia Cheng, Yi Fan, Shichao He, Shucai Li, Haoyu Ye, Caifeng Xie, Wenshuang Wu, Chunyan Li, Heying Pei, Luyuan Li, Zhe Wei, Aihua Peng, Yuquan Wei, Weimin Li, Lijuan Chen
To overcome drug resistance caused by apoptosis deficiency in patients with non-small cell lung carcinoma (NSCLC), there is a need to identify other means of triggering apoptosis-independent cancer cell death. We are the first to report that isogambogenic acid (iso-GNA) can induce apoptosis-independent autophagic cell death in human NSCLC cells. Several features of the iso-GNA-treated NSCLC cells indicated that iso-GNA induced autophagic cell death. First, there was no evidence of apoptosis or cleaved caspase 3 accumulation and activation...
January 9, 2015: Scientific Reports
Hyun-Kyu An, Kyoung-Sook Kim, Ji-Won Lee, Mi-Hyun Park, Hyung-In Moon, Shin-Ji Park, Ji-Sue Baik, Cheorl-Ho Kim, Young-Choon Lee
Anticancer properties and mechanisms of mimulone (MML), C-geranylflavonoid isolated from the Paulownia tomentosa fruits, were firstly elucidated in this study. MML prevented cell proliferation in a dose- and time-dependent way and triggered apoptosis through the extrinsic pathway in A549 human lung adenocarcinoma cells. Furthermore, MML-treated cells displayed autophagic features, such as the formation of autophagic vacuoles, a primary morphological feature of autophagy, and the accumulation of microtubule-associated protein 1 light chain 3 (LC3) puncta, another typical maker of autophagy, as determined by FITC-conjugated immunostaining and monodansylcadaverine (MDC) staining, respectively...
2014: PloS One
Kwang Sup So, Cheol Hyeon Kim, Jin Kyung Rho, Sun Ye Kim, Yun Jung Choi, Joon Seon Song, Woo Sung Kim, Chang Min Choi, Young Jin Chun, Jae Cheol Lee
Protein kinase CK2 has diverse functions promoting and maintaining cancer phenotypes. We investigated the effect of CK2 inhibition in lung cancer cells with T790M-mediated resistance to the EGFR-TK inhibitor. Resistant sublines of PC-9 to gefitinib (PC-9/GR) and erlotinib (PC-9/ER) were established by previous study, and T790M secondary mutation was found in both resistant sublines. A decrease of EGFR by siRNA treatment effectively controlled the growth of resistant cells, thus suggesting that they still have EGFR-dependency...
2014: PloS One
Haifeng Li, Baopeng Xing, Yulan Quan, Mingli Sun
OBJECTIVE: To investigate the effect of selective phosphatase inhibitors Salubrinal on autophagy and apoptosis in the lung tissue of rats with acute paraquat (PQ) poisoning, and to explore its mechanism. METHODS: 200 Wistar rats were randomly divided into four groups by randomized arrangement table formed by computer, with 50 rats in each group. PQ poisoning model was reproduced by one time gastric lavage with 1 mL of 40 mg/kg PQ solution followed by intraperitoneal injection of 1 mL normal saline (NS) once a day...
September 2014: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
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