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Autophagy and PI3K-Akt

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https://www.readbyqxmd.com/read/28092744/quercetin-induces-apoptosis-and-autophagy-in-primary-effusion-lymphoma-cells-by-inhibiting-pi3k-akt-mtor-and-stat3-signaling-pathways
#1
Marisa Granato, Celeste Rizzello, Maria Saveria Gilardini Montani, Laura Cuomo, Marina Vitillo, Roberta Santarelli, Roberta Gonnella, Gabriella D'Orazi, Alberto Faggioni, Mara Cirone
Quercetin, a bioflavonoid contained in several vegetables daily consumed, has been studied for long time for its antiinflammatory and anticancer properties. Quercetin interacts with multiple cancer-related pathways such as PI3K/AKT, Wnt/β-catenin and STAT3. These pathways are hyperactivated in primary effusion lymphoma (PEL), an aggressive B cell lymphoma whose pathogenesis is strictly linked to the oncogenic virus Kaposis' Sarcoma-associated Herpesvirus (KSHV). In this study, we found that quercetin inhibited PI3K/AKT/mTOR and STAT3 pathways in PEL cells, and as a consequence, it down-regulated the expression of the prosurvival cellular proteins such as c-FLIP, cyclin D1 and cMyc...
January 5, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28087295/postconditioning-induced-neuroprotection-mechanisms-and-applications-in-cerebral-ischemia
#2
REVIEW
Yan-Ying Fan, Wei-Wei Hu, Fang Nan, Zhong Chen
Ischemic postconditioning (PostC) is defined as a series of rapid intermittent interruptions of blood flow at the phase of reperfusion, which produces neuroprotection against cerebral ischemia/reperfusion injury via mobilizing the brain's own endogenous adaptive mechanisms. Now the concept of conventional ischemic PostC has been extended to limb remote ischemic PostC and chemical PostC with hypoxia, volatile anesthetic, CO2, etc. According to the different temporal profile of PostC, it is divided into rapid and delayed PostC...
January 10, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28078994/modulation-of-tumour-related-signaling-pathways-by-natural-pentacyclic-triterpenoids-and-their-semisynthetic-derivatives
#3
Andrey V Markov, Evgeniya B Logashenko, Marina A Zenkova
Pentacyclic triterpenoids are a large class of natural isoprenoids that are widely biosynthesized in higher plants. These compounds are potent anticancer agents that exhibit antiproliferative, antiangiogenic, antiinflammatory and proapoptotic activities. Although their effects on multiple pathways have been reported, unifying mechanisms of action have not yet been established. To date, a huge number of semisynthetic derivatives have been synthesized in different laboratories on the basis of triterpenoid scaffolds, and many have been assayed for their biological activities...
January 12, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28072480/free-fatty-acids-induce-autophagy-and-lox-1-upregulation-in-cultured-aortic-vascular-smooth-muscle-cells
#4
Cheng-I Cheng, Yueh-Hong Lee, Po-Han Chen, Yu-Chun Lin, Ming-Huei Chou, Ying-Hsien Kao
Elevation of free fatty acids (FFAs) is known to affect microvascular function and contribute to obesity-associated insulin resistance, hypertension, and microangiopathy. Proliferative and synthetic vascular smooth muscle cells (VSMCs) increase intimal thickness and destabilize atheromatous plaques. This study aimed to investigate whether saturated palmitic acid (PA) and monounsaturated oleic acid (OA) modulate autophagy activity, cell proliferation, and vascular tissue remodeling in an aortic VSMC cell line...
November 5, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28061438/combination-of-arsenic-trioxide-and-everolimus-rad001-synergistically-induces-both-autophagy-and-apoptosis-in-prostate-cancer-cells
#5
Sheng Tai, Lingfan Xu, Ming Xu, Ligang Zhang, Yangyang Zhang, Kaipin Zhang, Li Zhang, Chaozhao Liang
The inhibitor of PI3K-AKT-mTOR pathway, such as Rad001, has not shown therapeutic efficacy as a single agent in prostate cancer. Arsenic trioxide induces the autophagic pathway in prostate cancer cells. We identified Arsenic trioxide can synergize with Rad001 to induce cytotoxicity of prostate cancer cells. Moreover, we identified synergistic induction of autophagy and apoptosis as the underlying mechanism. This enhanced autophagic cell death is accompanied by increased Beclin1 mRNA stability as well as upregulation of ATG5-ATG12 conjugate, Beclin1, and LC3-2...
January 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28049093/regulation-of-different-components-from-ophiopogon-japonicus-on-autophagy-in-human-lung-adenocarcinoma-a549cells-through-pi3k-akt-mtor-signaling-pathway
#6
Juan Chen, Jiarui Yuan, Liqiang Zhou, Maomao Zhu, Ziqi Shi, Jie Song, Qingyu Xu, Guowen Yin, You Lv, Yi Luo, Xiaobin Jia, Liang Feng
Autophagy plays a dual role in the development of cancer, acting as both a tumor suppressor and a cell survival inducer. Ophiopogon japonicus (L.f) Ker-Gawl (OJ), as a traditional Chinese medicine, specially possesses remarkable anti-cancer activity in the clinical. Previously, studies have indicated that flavonoids (FOJ) and steroidal saponins (SSOJ) are the main active substances of OJ. However, the effects of FOJ and SSOJ on autophagy of A549 cells have not been fully elucidated. In this study, we found that the expressions of autophagy-related mediators (LC3-II/LC3-I ratio, Atg-3, Atg-7 and Beclin-1) were increased in A549 cells by the treatment with FOJ (7...
December 31, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28036273/nerve-growth-factor-induced-akt-mtor-activation-protects-the-ischemic-heart-via-restoring-autophagic-flux-and-attenuating-ubiquitinated-protein-accumulation
#7
Zhou-Guang Wang, Hao Li, Yan Huang, Rui Li, Xiao-Fan Wang, Li-Xia Yu, Xue-Qiang Guang, Lei Li, Hong-Yu Zhang, Ying-Zheng Zhao, Chunxiang Zhang, Xiao-Kun Li, Rong-Zhou Wu, Mao-Ping Chu, Jian Xiao
The dysregulation of autophagy is related to a variety of cardiovascular diseases, such as myocardial ischemia/reperfusion (I/R). Nerve growth factor (NGF) has been shown to have therapeutic potential in ischaemic heart injury. In this study, we demonstrate that NGF administration can accelerate autophagic flux and attenuate protein ubiquitination in myocardial I/R heart. Our results showed that NGF could restored heart function and decreased the apoptosis of cardiomyocytes which induced by myocardial I/R injury...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28000752/infergen-stimulated-macrophages-restrict-mycobacterium-tuberculosis-growth-by-autophagy-and-release-of-nitric-oxide
#8
Susanta Pahari, Nargis Khan, Mohammad Aqdas, Shikha Negi, Jagdeep Kaur, Javed N Agrewala
IFN alfacon-1 (Infergen) is a synthetic form of Interferon (IFN)-α2b. Infergen has immunomodulatory activity and is effective against hepatitis C virus. However, the effect of Infergen (IFG) on Mycobacterium tuberculosis (Mtb) has not yet been reported. Therefore, for the first time, we have studied the influence of IFG in constraining the survival of Mtb in human macrophages. We observed that IFG significantly enhanced the maturation and activation of macrophages. Further, it substantially augmented the secretion of IL-6, nitric oxide (NO) and antigen uptake...
December 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27928645/braf-v600e-dependent-role-of-autophagy-in-uveal-melanoma
#9
Yinu Zhao, Weibin Wang, Irene Min, Brian Wyrwas, Maureen Moore, Rasa Zarnegar, Thomas J Fahey
BACKGROUND: Autophagy can function in a dual role in cancer development and progression: It can be cytoprotective or contribute to cell death. Therefore, determining the contextual role of autophagy between these two opposing effects is important. So far, little is known about the role of autophagy in uveal melanoma. In the present study, we looked to investigate the autophagic process, as well as its effect on cell survival in uveal melanoma cell lines under stressed conditions (starvation)...
December 7, 2016: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/27916377/tetrahydrocurcumin-provides-neuroprotection-in-rats-after-traumatic-brain-injury-autophagy-and-the-pi3k-akt-pathways-as-a-potential-mechanism
#10
Yongyue Gao, Jie Li, Lingyun Wu, Chenhui Zhou, Qiang Wang, Xiang Li, Mengliang Zhou, Handong Wang
BACKGROUND: Tetrahydrocurcumin provides neuroprotection in multiple neurologic disorders by modulating oxidative stress, inflammatory responses, and autophagy. However, in traumatic brain injury (TBI), it is unclear whether a beneficial effect of tetrahydrocurcumin exists. In this study, we hypothesized that administration of tetrahydrocurcumin provides neuroprotection in a rat model of TBI. MATERIAL AND METHODS: Behavioral studies were performed by recording and analyzing beam-walking scores...
November 2016: Journal of Surgical Research
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
#11
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/27895729/celastrus-orbiculatus-extract-triggers-apoptosis-and-autophagy-via-pi3k-akt-mtor-inhibition-in-human-colorectal-cancer-cells
#12
Lin Yang, Yanqing Liu, Mei Wang, Yayun Qian, Xiaojun Dai, Yaodong Zhu, Jue Chen, Shiyu Guo, Tadashi Hisamitsu
Celastrus orbiculatus is used as a folk medicine in China for the treatment of numerous diseases. The ethyl acetate extract of Celastrus orbiculatus (COE) also displays a wide range of anti-cancer activities in the laboratory. However, the effectiveness of COE-induced autophagy and its mechanism of action in colorectal cancer cells have not been investigated thus far. The present study analyzed the effect of COE on HT-29 cell viability, apoptosis and autophagy using MTT assay, flow cytometry, transmission electron microscopy and western blotting...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27889779/tanshinone-iia-affects-autophagy-and-apoptosis-of-glioma-cells-by-inhibiting-phosphatidylinositol-3-kinase-akt-mammalian-target-of-rapamycin-signaling-pathway
#13
Lijuan Ding, Shudong Wang, Weiyao Wang, Peng Lv, Donghai Zhao, Feier Chen, Tianjiao Meng, Lihua Dong, Ling Qi
OBJECTIVE: To test the effects of Tanshinone IIA (Tan IIA) on cell viability, cycle, apoptosis, and autophagy of human glioma cell U251 by regulating phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signal pathway. METHODS: Tan IIA and PI3K agonist (740 Y-P) were used to treat glioma cells U251. MTT assay was used to assess cell viability and flow cytometry was used to detect cell apoptosis and cell cycle. The expressions of apoptosis-related proteins (Bcl-2 and Bax), autophagy-related proteins (LC3B and Beclin 1) and PI3K/Akt/mTOR signal pathway-associated proteins (p-PI3K, p-Akt and p-mTOR) were evaluated by Western blotting...
November 26, 2016: Pharmacology
https://www.readbyqxmd.com/read/27886437/the-microrna-99-family-modulates-hepatitis-b-virus-replication-by-promoting-igf-1r-pi3k-akt-mtor-ulk1-signaling-induced-autophagy
#14
Yong Lin, Wanyu Deng, Jinke Pang, Thekla Kemper, Jing Hu, Jian Yin, Jiming Zhang, Mengji Lu
MicroRNAs (miRNAs) are small highly conserved noncoding RNAs that are widely expressed in multicellular organisms and participate in the regulation of various cellular processes including autophagy and viral replication. Evidently, miRNAs are able to modulate host gene expression and thereby inhibit or enhance hepatitis B virus (HBV) replication. The miR-99 family members are highly expressed in the liver. Interestingly, the plasma levels of miR-99 family in the peripheral blood correspond with HBV DNA loads...
November 25, 2016: Cellular Microbiology
https://www.readbyqxmd.com/read/27885243/di-n-butyl-phthalate-induced-hypospadias-relates-to-autophagy-in-genital-tubercle-via-the-pi3k-akt-mtor-pathway
#15
Xiang Li, Jinhao Li, Ya Zhang, Yun Zhou
OBJECTIVE: To explore the mechanisms of hypospadias induced by in utero exposure to din-butyl phthalate (DBP). METHODS: Timed-pregnant Sprague-Dawley rats were administered 750 mg/kg of DBP by gavage from GD (gestation days) 13 to GD 18, whereas control group received corn oil. Genital tubercles (GTs) and blood samples were collected from male fetuses on GD 19. The serum testosterone concentration, apoptosis activity, autophagosomes and their related proteins (light chain 3 (LC3-I, LC3-II)), and sequestosomes (SQSTM1/p62) in the GTs were then measured...
November 22, 2016: Journal of Occupational Health
https://www.readbyqxmd.com/read/27882079/overexpression-of-caveolin-1-reduces-taxol-resistance-in-human-osteosarcoma-cells-by-attenuating-pi3k-akt-jnk-dependent-autophagy
#16
Jian Guan, Zhenchao Yuan, Juliang He, Zhenjie Wu, Bin Liu, Xiang Lin, Ligen Mo, Hao Mo
Caveolin-1 (CAV-1), which is an oncoprotein and a tumor suppressor, is highly expressed in normal osteoblasts. Although researchers have investigated its role in human osteosarcoma, the mechanism of caveolin-1 action in osteosarcoma remains unknown. In the present study, Saos-2 and U-2 OS cells were cultured with a continuous induction protocol of gradually increasing Taxol concentration for 6 months to establish drug-resistant cell lines. CAV-1 expression levels in osteosarcoma cells were detected via western blotting and quantitative polymerase chain reaction...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27879648/the-role-of-deoxycytidine-kinase-dck-in-radiation-induced-cell-death
#17
Rui Zhong, Rui Xin, Zongyan Chen, Nan Liang, Yang Liu, Shumei Ma, Xiaodong Liu
Deoxycytidine kinase (dCK) is a key enzyme in deoxyribonucleoside salvage and the anti-tumor activity for many nucleoside analogs. dCK is activated in response to ionizing radiation (IR)-induced DNA damage and it is phosphorylated on Serine 74 by the Ataxia-Telangiectasia Mutated (ATM) kinase in order to activate the cell cycle G2/M checkpoint. However, whether dCK plays a role in radiation-induced cell death is less clear. In this study, we genetically modified dCK expression by knocking down or expressing a WT (wild-type), S74A (abrogates phosphorylation) and S74E (mimics phosphorylation) of dCK...
November 21, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27878958/inhibition-of-orai1-mediated-ca-2-entry-enhances-chemosensitivity-of-hepg2-hepatocarcinoma-cells-to-5-fluorouracil
#18
Bao-Dong Tang, Xin Xia, Xiao-Fei Lv, Bei-Xin Yu, Jia-Ni Yuan, Xiao-Yi Mai, Jin-Yan Shang, Jia-Guo Zhou, Si-Jia Liang, Rui-Ping Pang
Increasing evidence supports that activation of store-operated Ca(2+) entry (SOCE) is implicated in the chemoresistance of cancer cells subjected to chemotherapy. However, the molecular mechanisms underlying chemoresistance are not well understood. In this study, we aim to investigate whether 5-FU induces hepatocarcinoma cell death through regulating Ca(2+) -dependent autophagy. [Ca(2+) ]i was measured using fura2/AM dye. Protein expression was determined by Western blotting and immunohistochemistry. We found that 5-fluorouracil (5-FU) induced autophagic cell death in HepG2 hepatocarcinoma cells by inhibiting PI3K/AKT/mTOR pathway...
November 23, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27866190/role-of-mcpip1-in-the-endothelial-mesenchymal-transition-induced-by-silica
#19
Jie Chao, Xingang Wang, Yuxia Zhang, Tiebing Zhu, Wei Zhang, Zewei Zhou, Jian Yang, Bing Han, Yusi Cheng, Xiaojie Tu, Honghong Yao
BACKGROUND: Silicosis is characterized by the accumulation of fibroblasts and the excessive deposition of extracellular matrix. Fibroblast generation via endothelial-mesenchymal transition (EndMT) is one process responsible for this accumulation of fibroblasts. However, the mechanisms underlying EndMT remain unknown. METHODS: Human umbilical vein endothelial cells (HUVECs) were exposed to SiO2 (50 µg/cm2). Specific endothelial and mesenchymal markers were evaluated using immunofluorescence and western blot analysis...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27863407/induction-of-mitochondria-mediated-apoptosis-and-pi3k-akt-mtor-mediated-autophagy-by-aflatoxin-b2-in-hepatocytes-of-broilers
#20
Binlong Chen, Diyan Li, Miao Li, Sichen Li, Kenan Peng, Xian Shi, Lanyun Zhou, Pu Zhang, Zhongxian Xu, Huadong Yin, Yan Wang, Xiaoling Zhao
Aflatoxins have been shown to induce hepatotoxicity in animal models, but the effects of aflatoxin B2 (AFB2) on broiler hepatocytes is unclear. This study aimed to investigate the effects of AFB2 on apoptosis and autophagy to provide an experimental basis for understanding the mechanism of aflatoxin-induced hepatotoxicity. One hundred-twenty Cobb500 broilers were allocated to four groups and exposed to 0 mg/kg, 0.2 mg/kg, 0.4 mg/kg, and 0.8 mg/kg of AFB2 per day for 21 d. AFB2 exerted potent proapoptotic and proautophagic effects on hepatocytes, with increased numbers of apoptotic and autophagic hepatocytes...
November 15, 2016: Oncotarget
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