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Autophagy and PI3K-Akt

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https://www.readbyqxmd.com/read/28524116/inhibition-of-autophagy-promotes-salinomycin-induced-apoptosis-via-reactive-oxygen-species-mediated-pi3k-akt-mtor-and-erk-p38-mapk-dependent-signaling-in-human-prostate-cancer-cells
#1
Kwang-Youn Kim, Kwang-Il Park, Sang-Hun Kim, Sun-Nyoung Yu, Sul-Gi Park, Young Woo Kim, Young-Kyo Seo, Jin-Yeul Ma, Soon-Cheol Ahn
Recently, the interplay between autophagy and apoptosis has become an important factor in chemotherapy for cancer treatment. Inhibition of autophagy may be an effective strategy to improve the treatment of chemo-resistant cancer by consistent exposure to chemotherapeutic drugs. However, no reports have clearly elucidated the underlying mechanisms. Therefore, in this study, we assessed whether salinomycin, a promising anticancer drug, induces apoptosis and elucidated potential antitumor mechanisms in chemo-resistant prostate cancer cells...
May 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28521459/cisplatin-regulates-cell-autophagy-in-endometrial-cancer-cells-via-the-pi3k-akt-mtor-signalling-pathway
#2
Qiongyan Lin, Yifeng Wang, Dunjin Chen, Xiujie Sheng, Juan Liu, Hanzhen Xiong
Endometrial cancer is the most common gynaecological malignancy encountered in developed countries and the second most common in the developing world. The five-year survival rate of patients with endometrial cancer diagnosed at a late stage is <30%. Therefore, it is critical to develop a suitable chemotherapeutic regimen for late-stage endometrial cancer. Cisplatin (CDDP) is a first-line chemotherapeutic drug for endometrial cancer chemotherapy. The present study investigated the molecular mechanism underlying the effect of CDDP on endometrial cancer from the perspective of cell autophagy...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28515304/ros-mediated-jnk-activation-contributes-to-hbx-induced-autophagy-via-regulating-beclin-1-bcl-2-interaction
#3
Linmao Zhong, Wanqin Shu, Wangbin Dai, Bo Gao, Sidong Xiong
Autophagy is closely associated with the regulation of Hepatitis B virus (HBV) replication. HBV X protein (HBx), a multifunctional regulator in HBV-associated biological processes, has been demonstrated to be crucial for the autophagy induction by HBV. However, the molecular mechanisms of autophagy induction by HBx, especially the signaling pathways involved, remain still elusive. In present investigation, we demonstrated that HBx induced autophagosome formation independent of class I phosphatidylinositol-3 kinase (PI3K)/AKT/mTOR signaling pathway...
May 17, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28502293/-wuwei-wentong-chubi-capsule-promotes-the-autophagy-in-synovial-tissue-of-adjuvant-induced-arthritis-rats-and-its-mechanism
#4
Hui Jiang, Xiaochuang Liu, Xiujuan Qin, Junmei Song, Jian Liu
Objective To evaluate the effect of Wuwei Wentong Chubi (WWWTCB) Capsule on the PI3K/AKT/mTOR signaling pathway in the synovial tissues of adjuvant-induced arthritis (AA) rats, and investigate its potential pharmacological mechanisms of treating rheumatoid arthritis. Methods Sixty Sprague Dawley (SD) rats were randomly assigned into six groups evenly: normal group, model group, WWWTCB groups at 0.80, 1.60, 3.20 g/kg body mass, and tripterygium glycosides tablet (TPT) group at 40 mg/kg body mass. Except for the normal group, the other five groups were induced into AA models with Complete Freund's Adjuvant (CFA)...
May 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28498433/curcumin-induces-apoptotic-cell-death-and-protective-autophagy-in-human-gastric-cancer-cells
#5
Wei Li, Ying Zhou, Jin Yang, Haining Li, Huanhuan Zhang, Ping Zheng
Curcumin possesses an anticancer effect against a wide assortment of tumors with selective cytotoxicity for tumor cells. However, the mechanism involved in the curcumin‑induced anticancer effect remain unclear. In the present study, we investigated the efficacy of curcumin against human gastric cancer cell growth and the molecular mechanism involved. Our results demonstrated that curcumin inhibited the viabilities of gastric cancer cell lines BGC-823, SGC-7901 and MKN-28 in both a time- and dose-dependent manner...
May 11, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28493079/tlr2-regulates-allergic-airway-inflammation-and-autophagy-through-pi3k-akt-signaling-pathway
#6
Xuqin Jiang, Lei Fang, Huimei Wu, Xiaodong Mei, Fang He, Peishan Ding, Rongyu Liu
Toll-like receptors (TLRs) are innate pattern recognition receptors that play a critical role in allergic inflammation, yet their contribution to autophagy in asthma remains poorly defined. Here, we investigate the role of Toll-like receptor 2 (TLR2) in phosphoinositide 3-kinases/protein kinase B (PI3K/Akt) pathway-mediated autophagy in ovalbumin-induced airway inflammation in mice. Wild-type (WT) and TLR2-knockout (TLR2(-/-)) C57BL/6 mice were ovalbumin-sensitized and ovalbumin-challenged. In ovalbumin-challenged WT mice, enhanced expression of TLR2 in lung tissue, remarkable inflammatory cell infiltrates, goblet cell hyperplasia, and increased mucus production were observed...
May 10, 2017: Inflammation
https://www.readbyqxmd.com/read/28478808/anticancer-activities-of-harmine-by-inducing-a-pro-death-autophagy-and-apoptosis-in-human-gastric-cancer-cells
#7
Chuan Li, Yihai Wang, Chunhua Wang, Xiaomin Yi, Mingya Li, Xiangjiu He
BACKGROUND: Harmine, a β-carboline alkaloid from Peganum harmala, has multiple anti-tumor activities, especially for its folk therapy for digestive system neoplasm. However, the underlying mechanism of harmine on gastric cancer remains unclear. PURPOSE: To illuminate the potential anti-tumor activity and mechanism of harmine against gastric cancer cells. METHODS/STUDY DESIGNS: The anti-proliferative activity of harmine in vitro was evaluated by MTT assay...
May 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28476020/the-role-of-autophagy-in-hepatocellular-carcinoma-friend-or-foe
#8
REVIEW
Lian Liu, Jia-Zhi Liao, Xing-Xing He, Pei-Yuan Li
Autophagy is an evolutionarily conserved lysosome-dependent catabolic process which degrades cell's components in order to recycle substrates to exert optimally and adapt to tough circumstances. It is a critical cellular homeostatic mechanism with stress resistance, immunity, antiaging, and pro-tumor or anti-tumor effects. Among these, the role of autophagy in cancer is the most eye-catching that is not immutable but dynamic and highly complex. Basal autophagy acts as a tumor suppressor by maintaining genomic stability in normal cells...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28475412/pi3k-akt-mtor-axis-sustains-rotavirus-infection-via-the-4e-bp1-mediated-autophagy-pathway-and-represents-an-antiviral-target
#9
Yuebang Yin, Wen Dang, Xinying Zhou, Lei Xu, Wenshi Wang, Wanlu Cao, Sunrui Chen, Junhong Su, Xuepeng Cai, Shaobo Xiao, Maikel P Peppelenbosch, Qiuwei Pan
Rotavirus infection is a major cause of severe dehydrating diarrhea in infants younger than five years old and in particular cases of immunocompromised patients irrespective to the age of the patients. Although vaccines have been developed, antiviral therapy is an important complement that cannot be substituted. Because of the lack of specific approved treatment, it is urgent to facilitate the cascade of further understanding of the infection biology, identification of druggable targets and the final development of effective antiviral therapies...
May 5, 2017: Virulence
https://www.readbyqxmd.com/read/28475179/mtorc1-independent-autophagy-regulates-receptor-tyrosine-kinase-phosphorylation-in-colorectal-cancer-cells-via-an-mtorc2-mediated-mechanism
#10
Aikaterini Lampada, James O'Prey, Gyorgy Szabadkai, Kevin M Ryan, Daniel Hochhauser, Paolo Salomoni
The intracellular autophagic degradative pathway can have a tumour suppressive or tumour-promoting role depending on the stage of tumour development. Upon starvation or targeting of oncogenic receptor tyrosine kinases (RTKs), autophagy is activated owing to the inhibition of PI3K/AKT/mTORC1 signalling pathway and promotes survival, suggesting that autophagy is a relevant therapeutic target in these settings. However, the role of autophagy in cancer cells where the PI3K/AKT/mTORC1 pathway is constitutively active remains partially understood...
June 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28459209/effects-of-endoplasmic-reticulum-stress-on-the-autophagy-apoptosis-and-chemotherapy-resistance-of-human-breast-cancer-cells-by-regulating-the-pi3k-akt-mtor-signaling-pathway
#11
Jia-Teng Zhong, Jian Yu, Hai-Jun Wang, Yu Shi, Tie-Suo Zhao, Bao-Xia He, Bin Qiao, Zhi-Wei Feng
Nowadays, although chemotherapy is an established therapy for breast cancer, the molecular mechanisms of chemotherapy resistance in breast cancer remain poorly understood. This study aims to explore the effects of endoplasmic reticulum stress on autophagy, apoptosis, and chemotherapy resistance in human breast cancer cells by regulating PI3K/AKT/mTOR signaling pathway. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to detect the cell viability of six human breast cancer cell lines (MCF-7, ZR-75-30, T47D, MDA-MB-435s, MDA-MB-453, and MDA-MB-231) treated with tunicamycin (5 µM), after which MCF-7 cells were selected for further experiment...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28451738/erratum-to-dioscin-induced-autophagy-mitigates-cell-apoptosis-through-modulation-of-pi3k-akt-and-erk-and-jnk-signaling-pathways-in-human-lung-cancer-cell-lines
#12
Ming-Ju Hsieh, Te-Lung Tsai, Yih-Shou Hsieh, Chau-Jong Wang, Hui-Ling Chiou
No abstract text is available yet for this article.
April 27, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28442505/overexpressed-fatty-acid-synthase-in-gastrointestinal-stromal-tumors-targeting-a-progression-associated-metabolic-driver-enhances-the-antitumor-effect-of-imatinib
#13
Chien-Feng Li, Fu-Min Fang, Yeng-Yang Chen, Ting-Ting Liu, Ti-Chun Chan, Shih-Chen Yu, Li-Tzong Chen, Hsuan-Ying Huang
Purpose: In gastrointestinal stromal tumors (GISTs), lipid-metabolizing enzymes remain underexplored, including fatty acid synthase (FASN). <p>Experimental Design: Forty GISTs were quantitated for FASN mRNA abundance. FASN immunoexpression was informative in 350 GISTs, including 213 with known KIT/PDGFRA/BRAF genotypes. In imatinib-resistant FASN-overexpressing GIST cells, the roles of overexpressed FASN and FASN-targeting C75 in tumor phenotypes, apoptosis and autophagy, KIT transcription, PI3K/AKT/mTOR activation, and imatinib resistance were analyzed by RNA interference or myristoylated-AKT transfection...
April 25, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28436000/foxo3a-suppression-and-vps34-activity-are-essential-to-anti-atrophic-effects-of-leucine-in-skeletal-muscle
#14
Igor L Baptista, João G Silvestre, William J Silva, Siegfried Labeit, Anselmo S Moriscot
Our aim is to gain insight into the mechanisms underlying the anti-atrophic effects of leucine, namely, the way that this amino acid can restrain the up-regulation of MuRF1 and Mafbx/Atrogin-1 in muscle atrophy. Male rats received dietary leucine supplementation for 1-3 days, during which time their hind limbs were immobilized. Our results showed that leucine inhibited Forkhead Box O3 (FoxO3a) translocation to cell nuclei. In addition, leucine was able to reverse the expected reduction of FoXO3a ubiquitination caused by immobilization...
April 24, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28435223/efficacy-of-the-dual-pi3k-and-mtor-inhibitor-nvp-bez235-in-combination-with-imatinib-mesylate-against-chronic-myelogenous-leukemia-cell-lines
#15
Pengliang Xin, Chuntuan Li, Yan Zheng, Qunyi Peng, Huifang Xiao, Yuanling Huang, Xiongpeng Zhu
BACKGROUND: Phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway is a therapy target of cancer. We aimed to confirm the effect of dual PI3K/mTOR inhibitor NVP-BEZ235 on proliferation, apoptosis, and autophagy of chronic myelogenous leukemia (CML) cells and sensitivity of tyrosine kinase inhibitor in vitro. METHODS: Two human CML cell lines, K562 and KBM7R (T315I mutant strain), were used. The proliferation of CML cells was detected by MTS (Owen's reagent) assay...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28433890/il-37-induces-autophagy-in-hepatocellular-carcinoma-cells-by-inhibiting-the-pi3k-akt-mtor-pathway
#16
Ting-Ting Li, Di Zhu, Tong Mou, Zhen Guo, Jun-Liang Pu, Qing-Song Chen, Xu-Fu Wei, Zhong-Jun Wu
Autophagy is an intracellular "self-eating" process that is closely related to inflammation and cellular immunity. New studies indicate that autophagy is also involved in tumor suppression. The anti-inflammatory cytokine interleukin-37 (IL-37) has been shown to have tumor-suppressive abilities in hepatocellular carcinoma (HCC). Notably, autophagy appears to play a dual role in the development of HCC and may be involved in both tumorigenesis and tumor suppression. However, the potential role of IL-37 in autophagy is currently unknown...
April 20, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28428363/phlpp-a-putative-cellular-target-during-insulin-resistance-and-type-2-diabetes
#17
Alpana Mathur, Vivek Kumar Pandey, Poonam Kakkar
Progressive research in the past decade converges to the impact of PHLPP (Pleckstrin homology domain and leucine rich repeat protein phosphatase) in regulating the cellular metabolism through PI3K/Akt inhibition. Defects in the PKB/Akt signaling coordinates with impaired insulin secretion and insulin resistance, identified during T2D, obesity and cardiovascular disorders which brings in the relevance of PHLPPs in the metabolic paradigm. In this review, we discuss the impact of PHLPP isoforms in insulin signaling and its associated cellular events including mitochondrial dysfunction, DNA damage, autophagy and cell death...
April 20, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28427045/mir-142-3p-overexpression-increases-chemo-sensitivity-of-nsclc-by-inhibiting-hmgb1-mediated-autophagy
#18
Yuqing Chen, Xin Zhou, Jianou Qiao, Aihua Bao
BACKGROUND: Non-small-cell lung cancer (NSCLC) is a deadly cancer with high mortality rate. Drug resistance represents a main obstacle in NSCLC treatment. High mobility group box-1 (HMGB1) protein promotes drug resistance in NSCLC cells by activating protective autophagy. METHODS: In the current study, we investigated the regulatory role of microRNA-142-3p (miR-142-3p) in HMGB1-mediated autophagy of NSCLC cells and its impact on drug resistance of NSCLC in vitro and in vivo...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28408883/alisol-a-24-acetate-and-alisol-b-23-acetate-induced-autophagy-mediates-apoptosis-and-nephrotoxicity-in-human-renal-proximal-tubular-cells
#19
Chunfei Wang, Liang Feng, Liang Ma, Haifeng Chen, Xiaobin Tan, Xuefeng Hou, Jie Song, Li Cui, Dan Liu, Juan Chen, Nan Yang, Jing Wang, Ying Liu, Bingjie Zhao, Gang Wang, Yuanli Zhou, Xiaobin Jia
Two natural compounds alisol A 24-acetate (24A) and alisol B 23-acetate (23B) are abundant in Rhizoma alismatis. In the present study, we evaluated the induction of 24A and 23B on apoptosis and possible nephrotoxicity of human renal proximal tubular (HK-2) cells by activating autophagy and also explored its regulation on PI3K/Akt/mTOR signaling pathway. Presently, Clusterin, Kim-1, and TFF-3 were considered to be new bioindicators of nephrotoxicity. Interestingly, the protein expression and mRNA levels of Clusterin, Kim-1 and TFF-3 could be significantly increased by 23B and 24A in vivo and in vitro...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28408137/4-acetylantroquinonol-b-suppresses-autophagic-flux-and-improves-cisplatin-sensitivity-in-highly-aggressive-epithelial-cancer-through-the-pi3k-akt-mtor-p70s6k-signaling-pathway
#20
Mingche Liu, Oluwaseun Adebayo Bamodu, Wen-Chien Huang, Muhammad Ary Zucha, Yen-Kuang Lin, Alexander T H Wu, Chun-Chih Huang, Wei-Hwa Lee, Chiou-Chung Yuan, M Hsiao, Li Deng, Yew-Min Tzeng, Chi-Tai Yeh
Targeting residual self-renewing, chemoresistant cancerous cells may represent the key to overcoming therapy resistance. The entry of these quiescent cells into an activated state is associated with high metabolic demand and autophagic flux. Therefore, modulating the autophagy pathway in aggressive carcinomas may be beneficial as a therapeutic modality. In this study, we evaluated the anti-tumor activities of 4-acetylantroquinonol B (4-AAQB) in chemoresistant ovarian cancer cells, particularly its ability to modulate autophagy through autophagy-related genes (Atg)...
April 10, 2017: Toxicology and Applied Pharmacology
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