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Autophagy and cancer

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https://www.readbyqxmd.com/read/29453806/cq-sensitizes-human-pancreatic-cancer-cells-to-gemcitabine-through-the-lysosomal-apoptotic-pathway-via-reactive-oxygen-species
#1
Zhiping Fu, Cheng Xi, Jie Kuang, Haoran Feng, Lingxie Chen, Juyong Liang, Xiaonan Shen, Stanley Yuen, Peng Chenghong, Shen Baiyong, Jin Zhijian, Weihua Qiu
As an established anti-cancer drug, gemcitabine (GEM) is an effective systemic treatment for advanced pancreatic cancer (PC). However, little is known about the potential effectors that may modify tumour cell sensitivity towards GEM. Autophagy, as a physiological cellular mechanism, is involved in both cell survival and cell death. In this study, we found that exposure to GEM induced a significant increase in autophagy in a dose-dependent manner in PANC-1 and BxPC-3 cells. Inhibition of autophagy by chloroquine (CQ) and ATG7 siRNA increased GEM-induced cytotoxicity, and CQ was more effective than ATG7 siRNA...
February 17, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29453315/autophagic-flux-is-regulated-by-interaction-between-the-c-terminal-domain-of-patched1-and-atg101
#2
Lucy X Chen, Cintli C Morales-Alcala, Natalia A Riobo-Del Galdo
The Hedgehog (Hh) receptor Patched1 (PTCH1) is a well-known tumor suppressor that in its active form represses Smoothened (SMO) activity, inhibits proliferation, and induces apoptosis. The cytoplasmic C-terminal domain (CTD) regulates PTCH1 turnover and nucleates a pro-apoptotic complex. In this study, it was mechanistically determined that Autophagy Related 10 (ATG101), essential for mammalian autophagy, physically interacts with the CTD of PTCH1 and connects it to the ULK complex, which stimulates the autophagy machinery in response to changes in nutrient availability...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29452093/autophagy-inhibition-enhances-anticancer-efficacy-of-artepillin-c-a-cinnamic-acid-derivative-in-brazilian-green-propolis
#3
Satoshi Endo, Manami Hoshi, Toshiyuki Matsunaga, Takahiro Inoue, Kenji Ichihara, Akira Ikari
Propolis, a resinous substance produced by honeybees, possesses various biological actions including anticancer activity towards tumor cells. Recently, the ethanol extract of Brazilian green propolis has been shown to induce autophagy, which is known to be induced in treatment of cancer cells with anticancer drugs, leading to cancer cell survival and decreased sensitivity to anticancer agents. In this study, we aimed to identify autophagy-inducing components of the propolis and elucidated the reciprocal relationship between anticancer cytotoxicity and protective autophagy in prostate cancer CWR22Rv1 cells...
February 13, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29449540/s100a4-promotes-lung-tumor-development-through-%C3%AE-catenin-pathway-mediated-autophagy-inhibition
#4
Shasha Hou, Tian Tian, Dianwen Qi, Kaiji Sun, Qi Yuan, Ziling Wang, Zhihai Qin, Zhenlong Wu, Zhinan Chen, Jinhua Zhang
Autophagy has emerged as a critical pathway in tumor development. S100A4 plays important roles in tumor metastasis, but its role in regulating autophagy has not been well characterized. In this study, we found that S100A4 was significantly upregulated in lung adenocarcinoma tissues. Clinical investigation demonstrated that high expression level of S100A4 was associated with tumor size and advanced tumor grades of lung adenocarcinoma patients. Moreover, our results revealed that extracellular S100A4 or overexpression of S100A4 inhibited starvation-induced autophagy and promoted cell proliferation in lung cancer cells in vitro; whereas small interfering RNA (siRNA)-mediated suppression of S100A4 increased autophagy and reduced cell viability in both A549 and LLC cells...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29448933/the-curious-case-of-vacuolar-atpase-regulation-of-signaling-pathways
#5
REVIEW
Sahithi Pamarthy, Arpita Kulshrestha, Gajendra K Katara, Kenneth D Beaman
The Vacuolar ATPase (V-ATPase) is a proton pump responsible for controlling the intracellular and extracellular pH of cells. The structure of V-ATPase has been highly conserved among all eukaryotic cells and is involved in diverse functions across species. V-ATPase is best known for its acidification of endosomes and lysosomes and is also important for luminal acidification of specialized cells. Several reports have suggested the involvement of V-ATPase in maintaining an alkaline intracellular and acidic extracellular pH thereby aiding in proliferation and metastasis of cancer cells respectively...
February 15, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29448055/proteomic-characterization-of-withaferin-a-targeted-protein-networks-for-the-treatment-of-monoclonal-myeloma-gammopathies
#6
Martin Dom, Fritz Offner, Wim Vanden Berghe, Xaveer Van Ostade
Withaferin A (WA), a natural steroid lactone from the plant Withania somnifera, is often studied because of its antitumor properties. Although many in vitro and in vivo studies have been performed, the identification of Withaferin A protein targets and its mechanism of antitumor action remain incomplete. We used quantitative chemoproteomics and differential protein expression analysis to characterize the WA antitumor effects on a multiple myeloma cell model. Identified relevant targets were further validated by Ingenuity Pathway Analysis and Western blot and indicate that WA targets protein networks that are specific for monoclonal gammopathy of undetermined significance (MGUS) and other closely related disorders, such as multiple myeloma (MM) and Waldenström macroglobulinemia (WM)...
February 12, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29445224/lup-20-29-en-3%C3%AE-28-di-yl-nitrooxy-acetate-affects-mcf-7-proliferation-through-the-crosstalk-between-apoptosis-and-autophagy-in-mitochondria
#7
Xiaoning Yan, Lei Yang, Gaili Feng, Zhuli Yu, Minjie Xiao, Weibin Cai, Yanmei Xing, Shasha Bai, Junqia Guo, Zhiyu Wang, Tao Wang, Rong Zhang
Betulin (BT), a pentacyclic lupine-type triterpenoid natural product, possesses antitumor activity in various types of cancers. However, its clinical development was discouraged due to its low biological activities and poor solubility. We prepared lup-20(29)-en-3β,28-di-yl-nitrooxy acetate (NBT), a derivative of BT, that was chemically modified at position 3 of ring A and C-28 by introducing a NO-releasing moiety. This study mainly explored the mechanism of NBT in treating breast cancer through the crosstalk between apoptosis and autophagy in mitochondria...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29445175/a-novel-autophagy-inhibitor-berbamine-blocks-snare-mediated-autophagosome-lysosome-fusion-through-upregulation-of-bnip3
#8
Ruoqiu Fu, Qin Deng, Hongwei Zhang, Xiaoye Hu, Yunong Li, Yanxia Liu, Jinjiao Hu, Qingsong Luo, Yanhao Zhang, Xiuxing Jiang, Lirong Li, Chong Yang, Ning Gao
Increasing evidences reveal that autophagy inhibitor could enhance the effect of chemotherapy to cancer. However, few autophagy inhibitors are currently approved for clinical application in humans. Berbamine (BBM) is a natural compound extracted from traditional Chinese medicine that is widely used for treatment of a variety of diseases without any obvious side effects. Here we found that BBM is a novel auophagy inhibitor, which potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human breast cancer cells...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29445107/progesterone-receptor-membrane-component-1-suppresses-the-p53-and-wnt-%C3%AE-catenin-pathways-to-promote-human-pluripotent-stem-cell-self-renewal
#9
Ji Yea Kim, So Young Kim, Hong Seo Choi, Min Kyu Kim, Hyun Min Lee, Young-Joo Jang, Chun Jeih Ryu
Progesterone receptor membrane component 1 (PGRMC1) is a multifunctional heme-binding protein involved in various diseases, including cancers and Alzheimer's disease. Previously, we generated two monoclonal antibodies (MAbs) 108-B6 and 4A68 against surface molecules on human pluripotent stem cells (hPSCs). Here we show that PGRMC1 is the target antigen of both MAbs, and is predominantly expressed on hPSCs and some cancer cells. PGRMC1 is rapidly downregulated during early differentiation of hPSCs. Although PGRMC1 knockdown leads to a spread-out morphology and impaired self-renewal in hPSCs, PGRMC1 knockdown hPSCs do not show apoptosis and autophagy...
February 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29444517/acetyl-coa-synthetase-2-promotes-cell-migration-and-invasion-of-renal-cell-carcinoma-by-upregulating-lysosomal-associated-membrane-protein-1-expression
#10
Lv Yao, Xiaoqiang Guo, Yaoting Gui
BACKGROUND/AIMS: Reprogramming energy metabolism is an emerging hallmark of many cancers, and this alteration is especially evident in renal cell carcinomas (RCCs). However, few studies have been conducted on lipid metabolism. This study investigated the function and mechanism of lipid metabolism-related acetyl-CoA synthetase 2 (ACSS2) in RCC development, cell migration and invasion. METHODS: Quantitative real-time PCR (qRT-PCR) was used to determine the expression of ACSS2 in cancer tissue and adjacent tissue...
February 8, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29443878/skeletal-muscle-pathophysiology-the-emerging-role-of-spermine-oxidase-and-spermidine
#11
REVIEW
Manuela Cervelli, Alessia Leonetti, Guglielmo Duranti, Stefania Sabatini, Roberta Ceci, Paolo Mariottini
Skeletal muscle comprises approximately 40% of the total body mass. Preserving muscle health and function is essential for the entire body in order to counteract chronic diseases such as type II diabetes, cardiovascular diseases, and cancer. Prolonged physical inactivity, particularly among the elderly, causes muscle atrophy, a pathological state with adverse outcomes such as poor quality of life, physical disability, and high mortality. In murine skeletal muscle C2C12 cells, increased expression of the spermine oxidase (SMOX) enzyme has been found during cell differentiation...
February 14, 2018: Medical Sciences: Open Access Journal
https://www.readbyqxmd.com/read/29440631/inhibition-of-kras-dependent-lung-cancer-cell-growth-by-deltarasin-blockage-of-autophagy-increases-its-cytotoxicity
#12
Elaine Lai Han Leung, Lian Xiang Luo, Zhong Qiu Liu, Vincent Kam Wai Wong, Lin Lin Lu, Ying Xie, Ni Zhang, Yuan Qing Qu, Xing Xing Fan, Ying Li, Min Huang, Dai Kai Xiao, Jun Huang, Yan Ling Zhou, Jian Xing He, Jian Ding, Xiao Jun Yao, David C Ward, Liang Liu
Deltarasin is a recently identified small molecule that can inhibit KRAS-PDEδ interactions by binding to a hydrophobic pocket on PDEδ, resulting in the impairment of cell growth, KRAS activity, and RAS/RAF signaling in human pancreatic ductal adenocarcinoma cell lines. Since KRAS mutations are the most common oncogene mutations in lung adenocarcinomas, implicated in over 30% of all lung cancer cases, we examined the ability of deltarasin to inhibit KRAS-dependent lung cancer cell growth. Here, for the first time, we document that deltarasin produces both apoptosis and autophagy in KRAS-dependent lung cancer cells in vitro and inhibits lung tumor growth in vivo...
February 13, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29439841/investigation-of-cancer-associated-fibroblasts-and-p62-expression-in-oral-cancer-before-and-after-chemotherapy
#13
Lizhong Liang, Haiji Luo, Qifen He, Yingying You, Yunping Fan, Jun Liang
PURPOSE: The aim of this study is to investigate the expression of the autophagy protein p62 in oral squamous cell carcinoma (OSCC) cells before and after chemotherapy. We also detected cancer-associated fibroblasts (CAFs) in these OSCC samples to explore the roles of p62 and CAFs in chemotherapy. MATERIALS AND METHODS: Immunohistochemistry was used to analyze the expression of p62 and α-SMA in 26 paired OSCC samples before and after chemotherapy. The relationships between clinicopathological features, clinical outcome and the expression of these proteins were analyzed...
January 12, 2018: Journal of Cranio-maxillo-facial Surgery
https://www.readbyqxmd.com/read/29439667/impact-of-pkc%C3%AE%C2%B5-downregulation-on-autophagy-in-glioblastoma-cells
#14
Ewa Toton, Aleksandra Romaniuk, Natalia Konieczna, Johann Hofmann, Jan Barciszewski, Maria Rybczynska
BACKGROUND: Several efforts have been focused on identification of pathways involved in malignancy, progression, and response to treatment in Glioblastoma (GB). Overexpression of PKCε was detected in histological samples from GB, anaplastic astrocytoma, and gliosarcoma and is considered an important marker of negative disease outcome. In multiple studies on GB, autophagy has been shown as a survival mechanism during cellular stress, contributing to resistance against anti-cancer agents...
February 13, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29439314/effects-of-malat1-on-proliferation-and-apo-ptosis-of-human-non-small-cell-lung-cancer-a549-cells-in-vitro-and-tumor-xenograft-growth-in-vivo-by-modulating-autophagy
#15
Jun Ma, Kaiming Wu, Kuanzhi Liu, Rong Miao
OBJECTIVE: To explore the ability of MALAT1 to influence non-small cell lung cancer (NSCLC) A549 cells in vitro and tumor xenograft growth in vivo by modulating autophagy. METHODS: LncRNA MALAT-1 in normal HBE cells and human NSCLC cells was measured. A549 cells were treated with si-MALAT-1, negative control and si-MALAT-1 + rapamycin. The mRNA levels of MALAT-1, P62 and LC3 was determined by the qRT-PCR and the protein levels of autophagy-related proteins by the western blotting...
January 29, 2018: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29438998/hydroxychloroquine-a-physiologically-based-pharmacokinetic-model-in-the-context-of-cancer-related-autophagy-modulation
#16
Keagan P Collins, Kristen M Jackson, Daniel L Gustafson
Hydroxychloroquine (HCQ) is a lysosomotropic autophagy inhibitor being used in over 50 clinical trials either alone or in combination with chemotherapy. Pharmacokinetic (PK) and pharmacodynamic (PD) studies with HCQ have shown that drug exposure in the blood does not correlate with autophagy inhibition in either peripheral blood mononuclear cells (PBMCs) or tumor tissue. To better explain this PK/PD disconnect a physiologically-based pharmacokinetic model (PBPK) was developed for HCQ describing the tissue-specific absorption, distribution, metabolism, and excretion as well as lysosome-specific sequestration...
February 8, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29438677/autophagy-inducers-in-cancer
#17
Maria Russo, Gian Luigi Russo
Autophagy is a complex, physiological process devoted to degrade and recycle cellular components. Proteins and organelles are first phagocytized by autophagosomes, then digested in lysosomes, and finally recycled to be utilized again during cellular metabolism. Moreover, autophagy holds an important role in the physiopathology of several diseases. In cancer, excellent works demonstrated the dual functions of autophagy in tumor biology: autophagy activation can promote cancer cells survival (protective autophagy), or contribute to cancer cell death (cytotoxic/nonprotective autophagy)...
February 10, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29436677/-retracted-apogossypolone-inhibits-the-proliferation-of-lncap-cells-in%C3%A2-vitro-and-in%C3%A2-vivo
#18
Xianqing Zhang, Xingbin Hu, Shijie Mu, Yonghua Zhan, Qunxing An, Zhixin Liu, Xiaofeng Huang
An interested reader drew to the attention of the Editorial Board of Molecular Medicine Reports that certain data in the above paper had already been published in a previous study featuring several of the same authors [Zhang XQ, Huang XF, Hu XB, Zhan YH, An QX, Yang SM, Xia AJ, Yi J, Chen R, Mu SJ and Wu DC: "Apogossypolone, a novel inhibitor of antiapoptotic Bcl-2 family proteins, induces autophagy of PC-3 and LNCaP prostate cancer cells in vitro". Asian J Androl 12: 697-708, 2010]. Specifically, Figs...
February 8, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29436654/tetrahydrocurcumin%C3%A2-induced-autophagy-via-suppression-of-pi3k-akt-mtor-in-non%C3%A2-small-cell-lung-carcinoma-cells
#19
Guoqiang Song, Honghui Lu, Fei Chen, Youmei Wang, Weibin Fan, Weifang Shao, Huoquan Lu, Bin Lin
Lung carcinoma is the leading cause of mortality due to cancer worldwide. Autophagy has a significant role in the development and progression of non‑small cell lung carcinoma (NSCLC). A previous study has revealed that tetrahydrocurcumin (THC), a traditional Chinese medicine isolated from Curcuma wenyujin (Chen & Ling, 1981), induces autophagy in human A549 NSCLC cells. The present study evaluated THC‑induced autophagy in A549 cells using various assays, including the Cell Counting Kit‑8, acridine orange staining, flow cytometry, reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), and western blot analysis of the markers of autophagy...
February 13, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29436618/role-of-autophagy-in-breast-cancer-and-breast-cancer-stem-cells-review
#20
Yanyan Han, Shujun Fan, Tao Qin, Jinfeng Yang, Yan Sun, Ying Lu, Jun Mao, Lianhong Li
Autophagy is a key catabolic process, in which cytosolic cargo is engulfed by the formation of a double membrane and then degraded through the fusing of autophagosomes with lysosomes. Autophagy is a constitutively active, evolutionarily conserved, catabolic process important for the maintenance of homeostasis in cellular stress responses and cell survival. Although the mechanisms of autophagy have not yet been fully elucidated, emerging evidence suggests that it plays a dual role in breast cancer and in maintaining the activity of breast cancer stem cells (CSCs)...
February 8, 2018: International Journal of Oncology
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