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Autophagy and PI3K-Akt

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https://www.readbyqxmd.com/read/28631572/endoplasmic-reticulum-stress-could-induce-autophagy-and-apoptosis-and-enhance-chemotherapy-sensitivity-in-human-esophageal-cancer-ec9706-cells-by-mediating-pi3k-akt-mtor-signaling-pathway
#1
Fang Zhou, Yan-Hua Li, Jian-Jun Wang, Jia Pan, Hong Lu
The study was designed to explore the mechanism of tunicamycin-induced endoplasmic reticulum stress in human esophageal cancer EC9706 cells and EC109 cells, as well as its effects on cell autophagy, apoptosis, and chemoresistance. Tunicamycin-induced endoplasmic reticulum stress model was established in EC9706 and EC109 cell lines. Western blotting was employed to detect the expression of endoplasmic reticulum stress iconic protein GRP78. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to evaluate the effect of different cisplatin and tunicamycin concentrations on survival rate of EC9706 cells and EC109 cells...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28623712/deoxypodophyllotoxin-induces-cytoprotective-autophagy-against-apoptosis-via-inhibition-of-pi3k-akt-mtor-pathway-in-osteosarcoma-u2os-cells
#2
Sang-Hun Kim, Kyo-Min Son, Kwang-Youn Kim, Sun-Nyoung Yu, Sul-Gi Park, Young-Wook Kim, Hyo-Won Nam, Jeung-Tak Suh, Jae-Hoon Ji, Soon-Cheol Ahn
BACKGROUND: A natural compound deoxypodophyllotoxin (DPT) possesses potent anti-proliferative and anti-tumor properties on several cancer types. It triggers cell cycle arrest followed by apoptosis through various cellular processes. However, it is limited to the action mechanism of DPT-mediated cell death modes via apoptosis and autophagy. METHODS: Cell viability assay, morphological changes, annexin-V/propidium iodide (PI) assay, reactive oxygen species (ROS), acridine orange staining, and Western blot analyses were evaluated...
April 13, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28599295/inhibition-of-the-pi3k-akt-mtor-pathway-activates-autophagy-and-compensatory-ras-raf-mek-erk-signalling-in-prostate-cancer
#3
Dominika E Butler, Christopher Marlein, Hannah F Walker, Fiona M Frame, Vincent M Mann, Matthew S Simms, Barry R Davies, Anne T Collins, Norman J Maitland
The PI3K/AKT/mTOR pathway is frequently activated in advanced prostate cancer, due to loss of the tumour suppressor PTEN, and is an important axis for drug development. We have assessed the molecular and functional consequences of pathway blockade by inhibiting AKT and mTOR kinases either in combination or as individual drug treatments. In established prostate cancer cell lines, a decrease in cell viability and in phospho-biomarker expression was observed. Although apoptosis was not induced, a G1 growth arrest was observed in PTEN null LNCaP cells, but not in BPH1 or PC3 cells...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28598230/protective-mechanism-of-fsh-against-oxidative-damage-in-mouse-ovarian-granulosa-cells-by-repressing-autophagy
#4
Ming Shen, Yi Jiang, Zhiqiang Guan, Yan Cao, Liechuan Li, Honglin Liu, Shao-Chen Sun
Oxidative stress-induced granulosa cell (GCs) death represents a common reason for follicular atresia. Follicle-stimulating hormone (FSH) has been shown to prevent GCs from oxidative injury, although the underlying mechanism remains to be elucidated. Here we first report that the suppression of autophagic cell death via some novel signaling effectors is engaged in FSH-mediated GCs protection against oxidative damage. The decline in GCs viability caused by oxidant injury was remarkably reduced following FSH treatment, along with impaired macroautophagic/autophagic flux under conditions of oxidative stress both in vivo and in vitro...
June 9, 2017: Autophagy
https://www.readbyqxmd.com/read/28597984/dual-inhibition-of-bdnf-trkb-and-autophagy-a-promising-therapeutic-approach-for-colorectal-cancer
#5
Clément Mazouffre, Sophie Geyl, Aurélie Perraud, Sabrina Blondy, Marie-Odile Jauberteau, Muriel Mathonnet, Mireille Verdier
Colorectal cancer (CRC) is the most common digestive cancer in the Western world. Despite effective therapies, resistance and/or recurrence frequently occur. The present study investigated the impact of two survival pathways-neurotrophic factors (TrkB/BDNF) and autophagy-on cell fate and tumour evolution. In vitro studies were performed on two CRC cell lines, SW480 (primary tumour) and SW620 (lymph node invasion), which were also used for subcutaneous xenografts on a nude mouse model. In addition, the presence of neurotrophic factors (NTs) and autophagy markers were assessed in tissue samples representative of different stages...
June 9, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28594401/upconversion-nanoparticle-mediated-photodynamic-therapy-induces-autophagy-and-cholesterol-efflux-of-macrophage-derived-foam-cells-via-ros-generation
#6
Xiaobo B Han, Hongxia X Li, Yueqing Q Jiang, Hao Wang, Xuesong S Li, Jiayuan Y Kou, Yinghong H Zheng, Zhongni N Liu, Hong Li, Jing Li, Dou Dou, You Wang, Ye Tian, Liming M Yang
Macrophage-derived foam cells are a major component of atherosclerotic plaques and have an important role in the progression of atherosclerotic plaques, thus posing a great threat to human health. Photodynamic therapy (PDT) has emerged as a therapeutic strategy for atherosclerosis. Here, we investigated the effect of PDT mediated by upconversion fluorescent nanoparticles encapsulating chlorin e6 (UCNPs-Ce6) on the cholesterol efflux of THP-1 macrophage-derived foam cells and explored the possible mechanism of this effect...
June 8, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28590019/afatinib-decreases-p-glycoprotein-expression-to-promote-adriamycin-toxicity-of-a549t-cells
#7
Yan Zhang, Chang-Yuan Wang, Ying-Jie Duan, Xiao-Kui Huo, Qiang Meng, Zhi-Hao Liu, Hui-Jun Sun, Xiao-Dong Ma, Ke-Xin Liu
We investigated the reversal effect of afatinib (AFT) on activity of adriamycin (ADR) in A549T cells and clarified the related molecular mechanisms. A549T cells overexpressing P-glycoprotein (P-gp) were resistant to anticancer drug ADR. AFT significantly increased the antitumor activity of ADR in A549T cells. AFT increased the intracellular concentration of ADR by inhibiting the function and expression of P-gp at mRNA and protein levels in A549T cells. Additionally, the reversal effect of AFT on P-gp mediated multidrug resistance (MDR) might be related to the inhibition of PI3K/Akt pathway...
June 7, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28588255/pkm2-promotes-cell-migration-and-inhibits-autophagy-by-mediating-pi3k-akt-activation-and-contributes-to-the-malignant-development-of-gastric-cancer
#8
Chao Wang, Jinling Jiang, Jun Ji, Qu Cai, Xuehua Chen, Yingyan Yu, Zhenggang Zhu, Jun Zhang
Pyruvate kinase M2 (PKM2) is a key kinase of glycolysis and is characteristic of all proliferating cells. The role of PKM2 in gastric cancer (GC) is still ambiguous and yet to be determined. To better understand the role of PKM2 in both the migration and invasion of GC, we measured the expression of PKM2 in GC cell lines using qRT-PCR and western blot. The prognostic value of PKM2 was analyzed by Immunohistochemistry in a cohort containing 88 GC patients. PKM2 was knocked down by the short hairpin RNA plasmid vector in NCI-N87 and BGC-823 cells, and the biological behavior and downstream signaling pathways were also investigated in vitro...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28583828/pkm2-mediated-inhibition-of-autophagy-facilitates-tat-s-inducing-hiv-1-transactivation
#9
Hong-Sheng Zhang, Zhong-Guo Zhang, Zhen Zhou, Guang-Yuan Du, Hu Li, Xiao-Ying Yu, Ying-Hui Huang
Considerable evidence has shown that autophagy has an important role in HIV-1 infection. However, it is still unknown whether metabolism-regulated autophagy pathway is involved in Tat-mediated HIV-1 transactivation. This study demonstrated that treatment of Tat in TZM-bl cells significantly down-regulated protein levels of Beclin-1, Atg-5, Atg-7, and LC3B-II and up-regulated of p62 levels. Blockage of autophagy enhanced Tat-induced HIV-1 transactivation in TZM-bl cells. Moreover, we found that Tat activated the Akt/mTOR and inhibited AMPK signaling pathway that was related to its up-regulation of PKM2 expression...
June 2, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28582759/%C3%AE-mangostin-inhibits-dmba-tpa-induced-skin-cancer-through-inhibiting-inflammation-and-promoting-autophagy-and-apoptosis-by-regulating-pi3k-akt-mtor-signaling-pathway-in-mice
#10
Fei Wang, Hongxia Ma, Zhaoguo Liu, Wei Huang, Xiaojing Xu, Xuemei Zhang
Skin cancer is the most common form of cancer responsible for considerable morbidity and mortality, the treatment progress of which remains slow though. Therefore, studies identifying anti-skin cancer agents that are innocuous are urgently needed. α-Mangostin, a natural product isolated from the pericarp of mangosteen fruit, has potent anti-cancer activity. However, its role in skin cancer remains unclear. The aim of this study was to evaluate the treatment effect of α-mangostin on skin tumorigenesis induced by 9,10-dimethylbenz[a]anthracene (DMBA)/TPA in mice and the potential mechanism...
June 2, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28581446/tregs-restrain-dendritic-cell-autophagy-to-ameliorate-autoimmunity
#11
Themis Alissafi, Aggelos Banos, Louis Boon, Tim Sparwasser, Alessandra Ghigo, Kajsa Wing, Dimitrios Vassilopoulos, Dimitrios Boumpas, Triantafyllos Chavakis, Ken Cadwell, Panayotis Verginis
Design of efficacious Treg-based therapies and establishment of clinical tolerance in autoimmune diseases have proven to be challenging. The clinical implementation of Treg immunotherapy has been hampered by various impediments related to the stability and isolation procedures of Tregs as well as the specific in vivo targets of Treg modalities. Herein, we have demonstrated that Foxp3+ Tregs potently suppress autoimmune responses in vivo through inhibition of the autophagic machinery in DCs in a cytotoxic T-lymphocyte-associated protein 4-dependent (CTLA4-dependent) manner...
June 5, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28577568/pirfenidone-inhibits-myofibroblast-differentiation-and-lung-fibrosis-development-during-insufficient-mitophagy
#12
Yusuke Kurita, Jun Araya, Shunsuke Minagawa, Hiromichi Hara, Akihiro Ichikawa, Nayuta Saito, Tsukasa Kadota, Kazuya Tsubouchi, Nahoko Sato, Masahiro Yoshida, Kenji Kobayashi, Saburo Ito, Yu Fujita, Hirofumi Utsumi, Haruhiko Yanagisawa, Mitsuo Hashimoto, Hiroshi Wakui, Yutaka Yoshii, Takeo Ishikawa, Takanori Numata, Yumi Kaneko, Hisatoshi Asano, Makoto Yamashita, Makoto Odaka, Toshiaki Morikawa, Katsutoshi Nakayama, Kazuyoshi Kuwano
BACKGROUND: Pirfenidone (PFD) is an anti-fibrotic agent used to treat idiopathic pulmonary fibrosis (IPF), but its precise mechanism of action remains elusive. Accumulation of profibrotic myofibroblasts is a crucial process for fibrotic remodeling in IPF. Recent findings show participation of autophagy/mitophagy, part of the lysosomal degradation machinery, in IPF pathogenesis. Mitophagy has been implicated in myofibroblast differentiation through regulating mitochondrial reactive oxygen species (ROS)-mediated platelet-derived growth factor receptor (PDGFR) activation...
June 2, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28577493/inhibition-of-pi3k-akt-mtor-signaling-pathway-protects-against-d-galactosamine-lipopolysaccharide-induced-acute-liver-failure-by-chaperone-mediated-autophagy-in-rats
#13
Yin Li, Ling Lu, Ning Luo, Yong-Qiang Wang, Hong-Mei Gao
OBJECTIVE: This study aims to investigate the effects of PI3K/AKt/mTOR signaling pathway on the proliferation and apoptosis in acute liver failure (ALF) by chaperone mediated autophagy (CMA). METHODS: The hepatocytes extracted from both normal rats and rats with ALF were assigned to control, acute injury, P13K agonist, and P13K inhibitor groups. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used as part of this investigation to detect the expression of PI3K/AKt/mTOR signaling pathway related-proteins (PI3K, AKt, mTOR), apoptosis related-proteins (Fas, Bax, Bcl-2), chaperone-mediated autophagy (CMA) marker proteins (LAMP-2A, HSC 70), p-PI3K, p-AKt, p-4E-BPI, and p-S6K...
May 31, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28574822/endoplasmic-reticulum-stress-induces-autophagy-and-apoptosis-while-inhibiting-proliferation-and-drug-resistance-in-multiple-myeloma-through-the-pi3k-akt-mtor-signaling-pathway
#14
Yun-Feng Fu, Xiao Liu, Meng Gao, Ya-Nan Zhang, Jing Liu
We investigated the effects of endoplasmic reticulum stress (ERS) on autophagy, proliferation, apoptosis, and drug resistance in multiple myeloma (MM). MM patients enrolled in our study (n = 268) were classified into sensitive and resistant groups based on chemotherapy efficacy, and their serum levels of β2-MG, albumin (ALB), lactic dehydrogenase (LDH), Ca2+ and hemoglobin were determined. In addition, human MM U266 and MOLP-2/R cells were divided into blank, tunicamycin (TM), TM + insulin-like growth factor-1 (IGF-1), and TM + rapamycin groups, and measured expression of ERS-related, PI3K/Akt/mTOR pathway-related, and autophagy-related mRNA and proteins...
May 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28573460/brain-glp-1-igf-1-signaling-and-autophagy-mediate-exendin-4-protection-against-apoptosis-in-type-2-diabetic-rats
#15
Emanuel Candeias, Inês Sebastião, Susana Cardoso, Cristina Carvalho, Maria Sancha Santos, Catarina Resende Oliveira, Paula I Moreira, Ana I Duarte
Type 2 diabetes (T2D) is a modern socioeconomic burden, mostly due to its long-term complications affecting nearly all tissues. One of them is the brain, whose dysfunctional intracellular quality control mechanisms (namely autophagy) may upregulate apoptosis, leading to cognitive dysfunction and Alzheimer disease (AD). Since impaired brain insulin signaling may constitute the crosslink between T2D and AD, its restoration may be potentially therapeutic herein. Accordingly, the insulinotropic anti-T2D drugs from glucagon-like peptide-1 (GLP-1) mimetics, namely, exendin-4 (Ex-4), could be a promising therapy...
June 2, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28560385/the-pi3k-akt-mtor-pathway-is-involved-in-cvb3-induced-autophagy-of-hela-cells
#16
Huan Chang, Xin Li, Qian Cai, Chunyun Li, Lang Tian, Jia Chen, Xiaowei Xing, Yu Gan, Wen Ouyang, Zuocheng Yang
Recent studies have found that viral myocarditis (VMC) associated with coxsackievirus B3 (CVB3) causes autophagy activation after infection, but the specific mechanism is not clear. The present study demonstrated that the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB)/mammalian target of rapamycin (mTOR) signaling pathway participates in CVB3‑induced autophagy. We found that the light chain 3 (LC3)‑Ⅱ/LC3‑I ratio was increased and p62 and p‑mTOR were altered at different times during CVB3 infection...
May 31, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28559999/hypoxia-inducible-factor-1-%C3%AE-protects-mesenchymal-stem-cells-against-oxygen-glucose-deprivation-induced-injury-via-autophagy-induction-and-pi3k-akt-mtor-signaling-pathway
#17
Bingke Lv, Tian Hua, Feng Li, Jianbang Han, Jie Fang, Limin Xu, Chengmei Sun, Zhongfei Zhang, Zhiming Feng, Xiaodan Jiang
Mesenchymal stem cell (MSC) transplantation is a promising therapeutic strategy for myocardial infarction. The survival rate of the grafted MSCs is limited by the conditions of hypoxia and low nutrient levels. In this study, we investigated the role of hypoxia-inducible factor 1 alpha (Hif-1α) in oxygen-glucose deprivation (OGD)-induced injury in MSCs. Hif-1α was overexpressed or suppressed in MSCs by transfection with a Hif-1α expressing vector or Hif-1α-specific siRNA, respectively. Then MSCs were exposed to OGD, and the changes in cell viability, cell cycle distribution and apoptosis were respectively monitored by MTT assay and flow cytometry...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28559961/autophagy-inhibitor-regulates-apoptosis-and-proliferation-of-synovial-fibroblasts-through-the-inhibition-of-pi3k-akt-pathway-in-collagen-induced-arthritis-rat-model
#18
Shu Li, Jin-Wei Chen, Xi Xie, Jing Tian, Cong Deng, Jia Wang, Hai-Na Gan, Fen Li
BACKGROUND AND OBJECTIVE: Mounting studies have illustrated an important role of autophagy in various diseases, but few studies have reported its contribution to rheumatoid arthritis (RA) and the underlying mechanism was largely unknown. This study aimed to investigate whether autophagy inhibitors could regulate apoptosis and proliferation through PI3K/AKT pathway in RA. METHODS: RA animal model was established by collagen induction. General observations and degree of joint swelling were observed...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28550454/oncogenic-roles-of-the-pi3k-akt-mtor-axis
#19
Masahiro Aoki, Teruaki Fujishita
The PI3K/AKT/mTOR pathway is frequently activated in various human cancers and has been considered a promising therapeutic target. Many of the positive regulators of the PI3K/AKT/mTOR axis, including the catalytic (p110α) and regulatory (p85α), of class IA PI3K, AKT, RHEB, mTOR, and eIF4E, possess oncogenic potentials, as demonstrated by transformation assays in vitro and by genetically engineered mouse models in vivo. Genetic evidences also indicate their roles in malignancies induced by activation of the upstream oncoproteins including receptor tyrosine kinases and RAS and those induced by the loss of the negative regulators of the PI3K/AKT/mTOR pathway such as PTEN, TSC1/2, LKB1, and PIPP...
May 28, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28537902/endoplasmic-reticulum-stress-promotes-autophagy-and-apoptosis-and-reverses-chemoresistance-in-human-ovarian-cancer-cells
#20
Jin-Long Hu, Xin-Long Hu, Ai-Ye Guo, Chao-Jie Wang, Yi-Yang Wen, Shun-Dong Cang
Ovarian cancer presents the highest mortality rate among gynecological tumors. Here, we measured cell viability, proliferation, apoptosis, autophagy, and expression of endoplasmic reticulum stress (ERS)-related proteins, PI3K/AKT/mTOR pathway-related proteins, and apoptosis- and autophagy-related proteins in SKOV3 and SKOV3/CDDP cells treated with combinations of CDDP, tunicamycin, and BEZ235 (blank control, CDDP, CDDP + tunicamycin, CDDP + BEZ235, and CDDP + tunicamycin + BEZ235). Increasing concentrations of tunicamycin and CDDP activated ERS in SKOV3 cells, reduced cell viability and proliferation, increased apoptosis and autophagy, enhanced expression of ERS-related proteins, and inhibited expression of PI3K/AKT/mTOR pathway-related proteins...
May 7, 2017: Oncotarget
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