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Autophagy and PI3K-Akt

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https://www.readbyqxmd.com/read/28747555/tripchlorolide-induces-autophagy-in-lung-cancer-cells-by-inhibiting-the-pi3k-akt-mtor-pathway-and-improves-cisplatin-sensitivity-in-a549-ddp-cells
#1
Li-Min Chen, Tian-Jiao Song, Jian-Hong Xiao, Zheng-Hui Huang, Yong Li, Ting-Yan Lin
Tripchlorolide (T4) has been shown to induce A549 lung cancer cell death predominantly by activating an autophagy pathway. However, the underlying mechanism remains unclear. Herein, we demonstrated that compared with T4 treatment alone, pretreatment with wortmannin (an inhibitor of phosphatidylinositol 3-kinase), perifosine (an inhibitor of AKT) or rapamycin (an inhibitor of mTOR) combined with a subsequent T4 treatment significantly impaired the cell viability of A549 and A549/DDP lung cancer cells. We found that either treatment scheme markedly reduced the activity of P13K and AKT...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28745544/euptox-a-induces-g1-arrest-and-autophagy-via-p38-mapk-and-pi3k-akt-mtor-mediated-pathways-in-mouse-splenocytes
#2
Quan Mo, Liwen Hu, Jiahua Weng, Yong Zhang, Yancheng C Zhou, Ruiguang Xu, Zhicai C Zuo, Junliang Deng, Zhihua Ren, Zhijun J Zhong, Guangneng Peng, Xiang Nong, Yahui Wei, Yanchun Hu
Euptox A (9-oxo-10, 11-dehydroageraphorone), the main toxin isolated from Eupatorium adenophorum, is known to induce immunotoxicity in animals. However, the precise mechanism underlying the effects of Euptox A on splenocytes is unclear. Here, we aimed to investigate the molecular mechanisms underlying the effect of Euptox A in mouse spleens after its intragastric administration and found that Euptox A exhibits proautophagic effects in splenocytes. Euptox A markedly arrested the splenocytes in the G0/G1 phase, which was accompanied by inhibition of the expression of the positive regulators CDK4, CDK2, cyclin D1, PCNA, and E2F1, and promotion of the expression of the negative regulators p53, p21 Waf1/Cip1, p27 Kip1, and Chk1...
July 1, 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/28739349/autophagy-protects-against-pi3k-akt-mtor-mediated-apoptosis-of-spinal-cord-neurons-after-mechanical-injury
#3
ZhenYu Wang, LinQuan Zhou, XiaoTing Zheng, Gang Chen, RongFeng Pan, JinHuang Li, WenGe Liu
Many studies have indicated that autophagy and apoptosis play an important role in the pathogenesis of spinal cord injury. In recent years, research on autophagy-related signal transduction pathways has demonstrated that the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway is closely associated with the initiation of autophagy. However, the mechanism of the pathological relationship between this signaling pathway and apoptosis in spinal cord injury is unclear...
July 21, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28731223/neferine-modulates-igf-1r-nrf2-signaling-in-doxorubicin-treated-h9c2-cardiomyoblasts
#4
Lohanathan Bharathi Priya, Rathinasamy Baskaran, Chih-Yang Huang, Viswanadha Vijaya Padma
Doxorubicin (DOX) induced cardiotoxicity is a major problem during chemotherapy of cancers. DOX-mediated suppression of type 1 IGF receptor (IGF-1R) signaling leads to cardiac dysfunction. Neferine, a bisbezylisoquinoline alkaloid from the seed embryos of Nelumbo nucifera Gaertn possesses a distinct range of pharmacological properties. Herewith, the present study attempts to elucidate the protective role of neferine against DOX induced toxicity in H9c2 rat cardiomyoblast cell line model. DOX-treated H9c2 cells significantly increased mitochondrial superoxide generation, depleted cellular antioxidant status, suppressed the activation of IGF-1R signaling via PI3K/Akt/mTOR and induced autophagy by the activation of ULK1, Beclin1, Atg7 and LC3B...
July 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28731179/clinical-significance-of-mir-138-in-patients-with-malignant-melanoma-through-targeting-of-pdk1-in-the-pi3k-akt-autophagy-signaling-pathway
#5
Fanjun Meng, Yuxia Zhang, Xing Li, Juan Wang, Zhiyu Wang
The present study investigated the clinical significance of miR-138 in patients with malignant melanoma (MM), which has previously been associated with tumor growth. In patients with MM, we found that the expression of miR-138 was significantly downregulated when compared with healthy control subjects. Overexpression of miR-138 in the human melanoma cell line A2058 inhibited cell proliferation and induced cell apoptosis, and increased caspase-3 and Bax protein expression when compared with a negative control group...
July 19, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28730764/mtor-deregulation-in-oral-cavity-squamous-cell-carcinoma
#6
Nicholas S Mastronikolis, Evangelos Tsiambas, Theodoros A Papadas, Panagiotis P Fotiades, Athanasios T Papadas, Stylianos N Mastronikolis, Ioannis Kastanioudakis, Vasileios Ragos
Signal transduction pathways consist of a variety of inter- and intra-cellular molecules. They act as supporting mechanisms for cell survival and homeostasis. Among them, the phosphatidylinositol 3-kinase (PI3K)/tumor suppressor phosphatase and tensin homologue deleted on chromosome ten (PTEN)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway plays a crucial role in regulating normal cell growth based on growth factor receptors (GFRs) interaction, including epidermal GFR (type II-HER2) and insulin GFR (IGF)...
May 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28728293/-curcumin-induces-apoptosis-and-protective-autophagy-in-human-gastric-cancer-cells-with-different-degree-of-differentiation
#7
W Li, Y Zhou, J Yang, H H Zhang, S L Zhao, T Zhang, J Huo, P Zheng
Objective: To investigate the effect of curcumin on the apoptosis and autophagy of human gastric cancer cells with different degree of differentiation. Methods: Gastric cancer cell lines BGC-823 and MKN-28 were treated with curcumin at different concentrations. The effect of curcumin on cell proliferation was measured by MTT assay. Apoptosis was assessed by flow cytometry. Autophagy status was analyzed by acridine orange staining. The expression levels of apoptotic and autophagy-related proteins were detected by Western blot...
July 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28706161/the-molecular-mechanisms-of-chemoresistance-in-cancers
#8
REVIEW
Hua-Chuan Zheng
Overcoming intrinsic and acquired drug resistance is a major challenge in treating cancer patients because chemoresistance causes recurrence, cancer dissemination and death. This review summarizes numerous molecular aspects of multi-resistance, including transporter pumps, oncogenes (EGFR, PI3K/Akt, Erk and NF-κB), tumor suppressor gene (p53), mitochondrial alteration, DNA repair, autophagy, epithelial-mesenchymal transition (EMT), cancer stemness, and exosome. The chemoresistance-related proteins are localized to extracellular ligand, membrane receptor, cytosolic signal messenger, and nuclear transcription factors for various events, including proliferation, apoptosis, EMT, autophagy and exosome...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28701921/endothelial-monocyte-activating-polypeptide-ii-suppresses-the-in-vitro-glioblastoma-induced-angiogenesis-by-inducing-autophagy
#9
Zhiqing Li, Jun Ma, Libo Liu, Xiaobai Liu, Ping Wang, Yunhui Liu, Zhen Li, Jian Zheng, Jiajia Chen, Wei Tao, Yixue Xue
The obstacle in delivering therapeutics to glioblastoma (GBM) is tumor-induced angiogenesis which leads to the formation of abnormal vessels and a dysfunctional blood-tumor barrier. Here, we elucidated the effect of endothelial-monocyte activating polypeptide II (EMAP II) on the GBM-induced angiogenesis as well as its potential mechanisms. Our results proved that EMAP II inhibited the viability, mitochondrial membrane potential, migration and tube formation of GBM-induced endothelial cells (GECs) by inducing cell autophagy, demonstrated by cell viability assay, JC-1 staining assay, transwell assay and tube formation assay, respectively...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28697535/cancer-stem-cells-and-epithelial-mesenchymal-transition-in-urothelial-carcinoma-possible-pathways-and-potential-therapeutic-approaches
#10
REVIEW
Dong Fang, Hiroshi Kitamura
There is growing evidence of the presence of cancer stem cells in urothelial carcinoma. Cancer stem cells have the ability to self-renew and to differentiate into all cell types of the original heterogeneous tumor. A panel of diverse cancer stem cell markers might be suitable for simulation studies of urothelial cancer stem cells and for the development of optimized treatment protocols. The present review focuses on the advances in recognizing the markers of urothelial cancer stem cells and possible therapeutic targets...
July 11, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28694352/protease-activated-receptor-2-promotes-kidney-tubular-epithelial-inflammation-by-inhibiting-autophagy-via-the-pi3k-akt-mtor-signalling-pathway
#11
Chunyang Du, Tao Zhang, Xia Xiao, Yonghong Shi, Huijun Duan, Yunzhuo Ren
Protease activated receptors 2 (PAR2), which belongs to a specific class of the G-protein-coupled receptors, are central to several inflammation processes. However, the precise molecular mechanism involved remains undefined. Autophagy has been previously shown to affect inflammation. In this study, we examine the effect of PAR2 on kidney tubular epithelial autophagy and on autophagy-related inflammation and reveal the underlying mechanism involved. Autophagic activity and levels of autophagic marker LC3 were examined in human kidney tubular epithelial cells with PAR2 knockdown or overexpression...
July 10, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28688896/the-alteration-of-autophagy-and-apoptosis-in-the-hippocampus-of-rats-with-natural-aging-dependent-cognitive-deficits
#12
Yang Yu, Linjing Feng, Junnan Li, Xiaoxin Lan, A Lixiang, Xiaoyan Lv, Ming Zhang, Li Chen
AIMS: The present study was aim to explore aging-dependent changes in hippocampal autophagy and apoptosis in a natural aging rat model from adult to old stages and to discover a suitable age for treating neurodegenerative diseases. METHODS: Wistar rats at 5, 18 and 24 months of age were used to mimic the adulthood, initial old, and old phases, respectively. The learning and cognitive ability of the rats was detected by the Morris water maze test. Morphological changes in the hippocampus were observed...
July 5, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28684964/apigenin-attenuates-adriamycin-induced-cardiomyocyte-apoptosis-via-the-pi3k-akt-mtor-pathway
#13
Wei Yu, Huirong Sun, Wenliang Zha, Weili Cui, Ling Xu, Qing Min, Jiliang Wu
Treatment with Adriamycin (ADR) is one of the major causes of chemotherapy-induced cardiotoxicity and therefore is the principal limiting factor in the effectiveness of chemotherapy for cancer patients. Apigenin (API) has been shown to play a cardioprotective role. The present study examined the effect of API on ADR-induced cardiotoxicity in mice. Sixty male Kunming mice were randomly divided into 4 groups: a control group, ADR model group, low-dose API treatment group (125 mg·kg(-1)), and high-dose API treatment group (250 mg·kg(-1))...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28683289/modulation-of-autophagy-by-bdnf-underlies-synaptic-plasticity
#14
Vassiliki Nikoletopoulou, Kyriaki Sidiropoulou, Emmanouela Kallergi, Yannis Dalezios, Nektarios Tavernarakis
Autophagy is crucial for neuronal integrity. Loss of key autophagic components leads to progressive neurodegeneration and structural defects in pre- and postsynaptic morphologies. However, the molecular mechanisms regulating autophagy in the brain remain elusive. Similarly, while it is widely accepted that protein turnover is required for synaptic plasticity, the contribution of autophagy to the degradation of synaptic proteins is unknown. Here, we report that BDNF signaling via the tropomyosin receptor kinase B (TrkB) and the phosphatidylinositol-3' kinase (PI3K)/Akt pathway suppresses autophagy in vivo...
July 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28677816/galangin-suppresses-human-laryngeal-carcinoma-via-modulation-of-caspase-3-and-akt-signaling-pathways
#15
Hai-Xu Wang, Chen Tang
Laryngeal cancers are mostly squamous cell carcinomas. Although targeting radio-resistant cancer cells is important for improving the treatmental efficiency, the signaling pathway- and therapeutic strategy-related to laryngeal carcinoma still require further study. Galangin is an active pharmacological ingredient, isolated from propolis and Alpinia officinarum Hance, and has been reported to have anticancer and anti-oxidative properties through regulation of cell cycle, resulting in angiogenesis, apoptosis, invasion and migration without triggering any toxicity in normal cells...
June 29, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28676397/feedback-autophagy-activation-as-a-key-resistance-factor-of-ku-0060648-in-colorectal-cancer-cells
#16
Mintao Mao, Yumei Liu, Xinhai Gao
The current study evaluated the potential anti-colorectal cancer (CRC) activity by Ku-0060648, a novel DNA-PKcs and PI3K duel inhibitor. In both CRC cell lines (HCT-116 and HT-29) and primary human colon cancer cells, Ku-0060648 exposure at nM concentrations efficiently inhibited cell proliferation. Meanwhile, Ku-0060648 provoked apoptosis in CRC cells. Ku-0060648 was yet ineffective to the normal colon epithelial cells. Ku-0060648 blocked PI3K-AKT-mTOR cascade and in-activated DNA-PKcs in CRC cells. Intriguingly, Ku-0060648 treatment induced feedback autophagy activation in HCT-116 cells...
July 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28672778/correction-h2o2-treatment-or-serum-deprivation-induces-autophagy-and-apoptosis-in-naked-mole-rat-skin-fibroblasts-by-inhibiting-the-pi3k-akt-signaling-pathway
#17
Shanmin Zhao, Li Li, Shiyong Wang, Chenlin Yu, Bang Xiao, Lifang Lin, Wei Cong, Jishuai Cheng, Wenjing Yang, Wei Sun, Shufang Cui
No abstract text is available yet for this article.
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28666254/the-pi3k-akt-pathway-a-critical-player-in-intervertebral-disc-degeneration
#18
REVIEW
Zhi-Hua Ouyang, Wen-Jun Wang, Yi-Guo Yan, Bin Wang, Guo-Hua Lv
Intervertebral disc degeneration (IDD) is thought to be the primary cause of low back pain, a severe public health problem worldwide. Current therapy for IDD aims to alleviate the symptoms and does not target the underlying pathological alternations within the disc. Activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway protects against IDD, which is attributed to increase of ECM content, prevention of cell apoptosis, facilitation of cell proliferation, induction or prevention of cell autophagy, alleviation of oxidative damage, and adaptation of hypoxic microenvironment...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28664142/molecular-mechanisms-of-anticancer-activity-of-deoxyelephantopin-in-cancer-cells
#19
Farha Arakkaveettil Kabeer, Dhanya Sethumadhavan Rajalekshmi, Mangalam Sivasankaran Nair, Remani Prathapan
BACKGROUND: Deoxyelephantopin (DOE) is a natural bioactive sesquiterpene lactone from Elephantopus scaber, a traditionally relevant herb in Chinese and Indian medicine. It has shown promising anticancer effects against a broad spectrum of cancers. METHODS: We examined the effect of DOE on growth, autophagy, apoptosis, cell cycle progression, metastasis, and various molecular signaling pathways in cancer cells, and endeavored to decipher the molecular mechanisms underlying its effect...
June 2017: Integrative medicine research
https://www.readbyqxmd.com/read/28660311/astragalus-polysaccharides-inhibits-cell-growth-and-pro-inflammatory-response-in-il-1%C3%AE-stimulated-fibroblast-like-synoviocytes-by-enhancement-of-autophagy-via-pi3k-akt-mtor-inhibition
#20
Qingliang Meng, Xuzhao Du, Huilian Wang, Huimin Gu, Junping Zhan, Zipeng Zhou
The hyperplastic growth of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) and inflammatory response are pathological hallmarks of RA. It has been reported that Astragalus polysaccharides (APS) possess appreciable anti-inflammatory activity against adjuvant-induced arthritis. Nevertheless, little is known about the role and detailed mechanism underlying the therapeutic effects of APS in RA. This study demonstrated that administration of APS dose-dependently impaired cell viability, increased cell apoptosis by decreasing Bcl-2 expression, increasing Bax expression and Caspase3 activity in IL-1β-stimulated RSC-364 cells and RA-FLS...
June 28, 2017: Apoptosis: An International Journal on Programmed Cell Death
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