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Autophagy and PI3K-Akt

Xiangyun Li, Xiangxiang Zhu, Chong Xu, Jianhua Wu
2-Methyl-2-butanol (MBT) is a chemical compound from the group of alcohols more specifically pentanols, which has shown an excellent anti-cancer activity in our previous study. However, its mechanism of action remains unclear. The present study was designed to investigate the anti-cancer effect of MBT on human retinoblastoma cells. The results showed that the use of MBT leads to HXO-RB44 cell death but is cytotoxic to normal cells at higher concentrations. It showed a dose- as well as a time-dependent inhibition of HXO-RB44 cells...
March 15, 2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Fang Guo, Yong Zou, Yongjiang Zheng
Moracin M, a phenolic component obtained from Mori Cortex, has been reported to have anti-inflammatory activities. The present study was designed to investigate the effects and mechanisms of Moracin M on lipopolysaccharide (LPS)-treated nucleus pulposus cells (NPCs) in intervertebral disc. NPCs were treated with moracin M at different concentrations for 1 h and then stimulated with LPS (0.5 μg/mL) for 24 h. The result demonstrated that moracin M could significantly inhibit LPS-induced inflammation. The elevated levels of IL-1β, TNF-α and IL-6 induced by LPS could be reversed by moracin M in NPCs...
March 17, 2018: International Immunopharmacology
Jun Zhang, Xiaohong Xiang, Shuangshuang Shu, Cuiling Zhang, Yuling Liang, Tingting Jiang, Wenying Zhang, Tingting Guo, Xiujie Liang, Xun Tang
It is well known that autophagy serves a crucial role in renal tubular epithelial cell (RTEC) injury in the pathogenesis of chronic kidney disease (CKD). The accumulation of advanced oxidation protein products (AOPPs) also participates in the progression of CKD. However, the effects of AOPPs on autophagy remain unknown. To clarify the underlying mechanism of RTEC injury in CKD, the effect of AOPPs on HK-2 cells, an RTEC cell line, was investigated. The results of the present study revealed that AOPP exposure downregulated the expression of B-cell lymphoma-2-interacting myosin-like coiled-coil protein 1, reduced the conversion of microtubule-associated proteins 1 light chain 3B (LC3)-I to LC3-II and the formation of autophagosomes, and lead to an accumulation of p62...
April 2018: Experimental and Therapeutic Medicine
Dongjia Lin, Yan Gao, Luodan Zhao, Yanhuo Chen, Shaofeng An, Zhixiang Peng
Enterococcus faecalis (E. faecalis) infection is considered an important etiological factor for the development of persistent apical periodontitis (PAP), but the exact mechanisms of autophagy between E. faecalis and immune cells remain unknown. In this study, we elucidated how E. faecalis lipoteichoic acid (LTA) is associated with macrophages autophagy. We found that E. faecalis LTA apparently activated macrophage autophagy with significant increase of autophagosomes and autophagy relative protein. Meanwhile, we noticed significantly decreasing expression of p-Akt and p-mTOR...
March 15, 2018: Biochemical and Biophysical Research Communications
Chengzheng Han, Guozheng Xing, Mengying Zhang, Min Zhong, Zhen Han, Chiyi He, Xiaoping Liu
Wogonoside, the main effective constituent of traditional Chinese medicine Scutellaria , belongs to the glucuronide family, with various functions, including detoxification, anti-inflammation and nourishing gallbladder, lowering blood pressure, diuresis and anti-allergic reactions. However, the effects of wogonoside on human colon cancer cells remain unclear. The present study aimed to investigate the anticancer effect of wogonoside on human colon cancer cells in vitro and its anticancer mechanisms. The results demonstrated that wogonoside significantly inhibited cell growth, induced apoptosis and mitochondrial-mediated autophagy of colon cancer cells...
April 2018: Oncology Letters
Jin-Cheng Huang, Zhi-Fei Cui, Shui-Mu Chen, Lian-Jun Yang, Hong-Kai Lian, Bin Liu, Zhi-Hai Su, Jin-Shi Liu, Min Wang, Zheng-Bo Hu, Jia-Yao Ouyang, Qing-Chu Li, Hai Lu
Osteosarcoma(OS) remains a major health concern in childhood and adolescence, although cisplatin is one of the gold standard chemotherapeutic drugs in the treatment of OS, chemoresistant to cisplatin is common. Phosphoinositide 3-kinase (PI3K)-Akt-mammalian target of rapamycin inhibitor (mTOR) pathway and autophagy regulates chemosensitivity incancer cells. In this study, we hypothesized that NVP-BEZ235, a dual inhibitor of PI3K/mTOR, could synergize cisplatin sensitivity in OS. In vitro , NVP-BEZ235 plus cisplatinexerted a synergistic effect on cell proliferation inhibition and apoptosis induction...
February 13, 2018: Oncotarget
Zhaomeng Wu, Qingyi Zhu, Yingying Yin, Dan Kang, Runyi Cao, Qian Tian, Yu Zhang, Shan Lu, Ping Liu
Traditional Chinese medicine (TCM) has a combined therapeutic result in cancer treatment by integrating holistic and local therapeutical effects, by which TCM can enhance the curative effect and reduce the side effect. In this study, we analyzed the effect of CFF-1 (alcohol extract from an anticancer compound Chinese medicine) on prostate cancer (PCa) cell lines and studied in detail the mechanism of cell death induced by CFF-1 in vitro and in vivo. From our data, we found for the first time that CFF-1 obviously arrested cell cycle in G1 phase, decreased cell viability and then increased nuclear rupture in a dose-dependent manner and finally resulted in apoptosis in prostate cancer cells...
March 13, 2018: Cancer Medicine
Mu-Lin Liu, Qiao Zhang, Xiao Yuan, Long Jin, Li-Li Wang, Tao-Tao Fang, Wen-Bin Wang
AIM: To investigate the role of long noncoding RNA (lncRNA) RP4 in colorectal cancer. METHODS: Lentivirus-mediated lncRNA RP4 overexpression and knockdown were performed in the colorectal cancer cell line SW480. Cell proliferation, tumor growth, and early apoptosis were evaluated by a cell counting kit-8 assay, an in vivo xenograft tumor model, and annexin V/propidium iodide staining, respectively. Analysis of the lncRNA RP4 mechanism involved assessment of the association of its expression with miR-7-5p and the SH3GLB1 gene...
March 7, 2018: World Journal of Gastroenterology: WJG
Yi-Yuan Zheng, Miao Wang, Xiang-Bing Shu, Pei-Yong Zheng, Guang Ji
AIM: To elucidate the potential role of autophagy and the protective effects of Jiang Zhi Granule (JZG) in metabolic stress-induced hepatocyte injury. METHODS: An in vitro and in vivo approach was used in this study. HepG2 cells were incubated in culture medium containing palmitate (PA; 0, 0.1, 0.2, 0.3, 0.4 or 0.5 mmol/L) and treated with or without JZG (100 μg/mL) for 24 h or 48 h, and the progression of autophagy was visualized by stable fluorescence-expressing cell lines LC3 and p62...
March 7, 2018: World Journal of Gastroenterology: WJG
Tiago Augusto, Georgina Correia-da-Silva, Cecília M P Rodrigues, Natércia Teixeira, Cristina Amaral
Aromatase inhibitors (AIs) are one of the principal therapeutic approaches for estrogen-receptor positive (ER+) breast cancer in postmenopausal women. They block estrogen biosynthesis through aromatase inhibition, thus preventing tumour progression. Besides the therapeutic success of the third-generation AIs, acquired-resistance may develop, leading to tumour relapse. This resistance is thought to be the result of a change in the behavior of ER in these breast cancer cells, presumably by PI3K/Akt pathway enhancement along with alterations in other signalling pathways...
March 12, 2018: Endocrine-related Cancer
Xianhua Gui, Lingyun Sun, Luo Gu, Hourong Cai, Hongwei Chen
Leptin, a protein-related product of the obesity gene, plays an important role in the pathogenesis of fibrotic diseases including pulmonary fibrosis. As a highly conservative process, autophagy regulates various biological functions. Otherwise, insufficient autophagy has been described in alveolar epithelial cells (AEC) to cope with the progression of pulmonary fibrosis. Hence, this study is to investigate the effects of leptin on fibrosis in TGF-β1 induced epithelial mesenchymal transition (EMT) and the potential roles of autophagy in this processes...
March 7, 2018: Biochemical and Biophysical Research Communications
Jin Xu, Yanqing Xia, Helong Zhang, Haibin Guo, Ke Feng, Cuilian Zhang
BACKGROUND: Preeclampsia (PE), characterized by hypertension and proteinuria, is a leading cause of perinatal and maternal mortality. Considering that mutation of H19 gene is closely associated with PE, we aimed to explore the functional role of long non-coding RNA H19 (lncRNA-H19) in trophoblast cells. METHODS: Expression of lncRNA-H19 in placenta tissues from patients with PE and healthy pregnant women after delivery was determined by quantitative reverse transcription PCR...
March 6, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Jeong-Hyeon Ko, Seok-Geun Lee, Woong Mo Yang, Jae-Young Um, Gautam Sethi, Srishti Mishra, Muthu K Shanmugam, Kwang Seok Ahn
Embelin is a naturally-occurring benzoquinone compound that has been shown to possess many biological properties relevant to human cancer prevention and treatment, and increasing evidence indicates that embelin may modulate various characteristic hallmarks of tumor cells. This review summarizes the information related to the various oncogenic pathways that mediate embelin-induced cell death in multiple cancer cells. The mechanisms of the action of embelin are numerous, and most of them induce apoptotic cell death that may be intrinsic or extrinsic, and modulate the NF-κB, p53, PI3K/AKT, and STAT3 signaling pathways...
March 9, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Jessica Lawrence, Richard Nho
The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR)-dependent pathway is one of the most integral pathways linked to cell metabolism, proliferation, differentiation, and survival. This pathway is dysregulated in a variety of diseases, including neoplasia, immune-mediated diseases, and fibroproliferative diseases such as pulmonary fibrosis. The mTOR kinase is frequently referred to as the master regulator of this pathway. Alterations in mTOR signaling are closely associated with dysregulation of autophagy, inflammation, and cell growth and survival, leading to the development of lung fibrosis...
March 8, 2018: International Journal of Molecular Sciences
Giuseppe Lamberti, Nicole Brighi, Ilaria Maggio, Lisa Manuzzi, Chiara Peterle, Valentina Ambrosini, Claudio Ricci, Riccardo Casadei, Davide Campana
The mechanistic target of rapamycin (mTOR) is part of the phosphoinositide-3-kinase (PI3K)/protein kinase B (AkT)/mTOR pathway and owes its name to the inhibitory effect of rapamycin. The mTOR has a central converging role for many cell functions, serving as a sensor for extracellular signals from energy status and nutrients availability, growth factors, oxygen and stress. Thus, it also modulates switch to anabolic processes (protein and lipid synthesis) and autophagy, in order to regulate cell growth and proliferation...
March 6, 2018: International Journal of Molecular Sciences
Jing Wu, Chao Sun, Ruoyi Wang, Juan Li, Meng Zhou, Mi Yan, Xia Xue, Chuanxin Wang
Cardiotoxicity is a dose-dependent side effect of epirubicin that restricts its clinical utility in cancer chemotherapy. Paeonol is an active constituent with various biological activities, including the protection of antineoplastic-induced toxicities. In the present study, we investigated the protective effect of paeonol on epirubicin-induced cardiotoxicity and explored the underlying mechanism. A series of methods were used including a MTT assay, flow cytometry, echocardiography, TUNEL staining, a dual-luciferase reporter assay, immunofluorescence, RT-PCR and Western blotting...
March 2, 2018: Chemico-biological Interactions
Dong-Qing Xu, Hidemi Toyoda, Xiao-Jun Yuan, Lei Qi, Vipin Shankar Chelakkot, Mari Morimoto, Ryo Hanaki, Kentarou Kihira, Hiroki Hori, Yoshihiro Komada, Masahiro Hirayama
Neuroblastoma (NB) is one of the most common solid tumors in children. High-risk NB remains lethal in about 50% of patients despite comprehensive and intensive treatments. Activation of PI3K/Akt/mTOR signaling pathway correlates with oncogenesis, poor prognosis and chemotherapy resistance in NB. Due to its central role in growth and metabolism, mTOR seems to be an important factor in NB, making it a possible target for NB. In this study, we investigated the effect of AZD8055, a potent dual mTORC1-mTORC2 inhibitor, in NB cell lines...
February 27, 2018: Experimental Cell Research
Maria J Perez-Alvarez, Mario Villa Gonzalez, Irene Benito-Cuesta, Francisco G Wandosell
Intense efforts are being undertaken to understand the pathophysiological mechanisms triggered after brain ischemia and to develop effective pharmacological treatments. However, the underlying molecular mechanisms are complex and not completely understood. One of the main problems is the fact that the ischemic damage is time-dependent and ranges from negligible to massive, involving different cell types such as neurons, astrocytes, microglia, endothelial cells, and some blood-derived cells (neutrophils, lymphocytes, etc...
2018: Frontiers in Neuroscience
Jiangang Liu, Yingru Xing, Ling Rong
A number of miRNAs have been found to be abnormally expressed or mutated in numerous cancers and thus, are considered to act as oncogenes or tumor suppressor genes. The aim of the present study was to investigate the effect of miR-181 on cisplatin-resistant non-small cell lung cancer (NSCLC). In patients with cisplatin-resistant NSCLC, miR-181 expression was found to be markedly decreased. In addition, in the cisplatin-resistant human lung adenocarcinoma cell line A549/DDP, miR-181 downregulation promoted cell growth and metastasis and inhibited cell apoptosis, whereas miR-181 overexpression exerted the opposite effects...
February 13, 2018: Oncology Reports
Yasuyo Urasaki, Chi Zhang, Ji-Xin Cheng, Thuc T Le
Current assessment of non-alcoholic fatty liver disease (NAFLD) with histology is time-consuming, insensitive to early-stage detection, qualitative, and lacks information on etiology. This study explored alternative methods for fast and quantitative assessment of NAFLD with hyperspectral stimulated Raman scattering (SRS) microscopy and nanofluidic proteomics. Hyperspectral SRS microscopy quantitatively measured liver composition of protein, DNA, and lipid without labeling and sensitively detected early-stage steatosis in a few minutes...
February 26, 2018: Scientific Reports
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