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Autophagy and cancer

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https://www.readbyqxmd.com/read/28531218/autophagy-inhibitor-facilitates-gefitinib-sensitivity-in-vitro-and-in-vivo-by-activating-mitochondrial-apoptosis-in-triple-negative-breast-cancer
#1
Zhaoyun Liu, Kewen He, Qinghua Ma, Qian Yu, Chenyu Liu, Isabella Ndege, Xinzhao Wang, Zhiyong Yu
Epidermal growth factor receptor (EGFR) is over-expressed in about 50% of Triple negative breast cancers (TNBCs), but EGFR inhibitors have not been effective in treating TNBC patients. Increasing evidence supports that autophagy was related to drug resistance at present. However, the role and the mechanism of autophagy to the treatment of TNBC remain unknown. In the current study, we investigated the effect of autophagy inhibitor to gefitinib (Ge) in TNBC cells in vitro and in nude mice vivo. Our study demonstrated that inhibition of autophagy by 3-Methyladenine or bafilomycin A1 improved Ge's sensitivity to MDA-MB-231 and MDA-MB-468 cells, as evidence from stronger inhibition of cell vitality and colony formation, higher level of G0/G1 arrest and DNA damage, and these effects were verified in nude mice vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28531143/a-4-phenoxyphenol-derivative-exerts-inhibitory-effects-on-human-hepatocellular-carcinoma-cells-through-regulating-autophagy-and-apoptosis-accompanied-by-downregulating-%C3%AE-tubulin-expression
#2
Wen-Tsan Chang, Wangta Liu, Yi-Han Chiu, Bing-Hung Chen, Shih-Chang Chuang, Yen-Chun Chen, Yun-Tzh Hsu, Mei-Jei Lu, Shean-Jaw Chiou, Chon-Kit Chou, Chien-Chih Chiu
Hepatocellular carcinoma (HCC) is a leading cancer worldwide. Advanced HCCs are usually resistant to anticancer drugs, causing unsatisfactory chemotherapy outcomes. In this study, we showed that a 4-phenoxyphenol derivative, 4-[4-(4-hydroxyphenoxy)phenoxy]phenol (4-HPPP), exerts an inhibitory activity against two HCC cell lines, Huh7 and Ha22T. We further investigated the anti-HCC activities of 4-HPPP, including anti-proliferation and induction of apoptosis. Our results showed that higher dosage of 4-HPPP downregulates the expression of α-tubulin and causes nuclear enlargement in both the Huh-7 and Ha22T cell lines...
May 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28529589/tetrandrine-triggers-an-alternative-autophagy-in-du145-cells
#3
Wei Qiu, Ai-Li Zhang, Ye Tian
Tetrandrine (Tet), a potent lysosomal inhibitor, blocks autophagic flux and induces cancer cell death. Previously, the present authors identified the prostate cancer cell line DU145 to exhibit high sensitivity towards Tet in 11 cancer cell lines. In the present study, autophagy in Tet-treated DU145 cells was investigated. Similar to other cell lines, such as PC-3 and 786-O cells, Tet neutralized the acidity of lysosome and blocked autophagy in DU145 cells. However, Tet failed to induce microtubule-associated protein 1 light chain 3 (LC3) conversion in DU145 cells...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28529582/angiotensin-ii-receptor-blockers-induce-autophagy-in-prostate-cancer-cells
#4
Yunseo Woo, Yu-Jin Jung
Angiotensin II receptor blockers (ARBs) are anti-hypertensive drugs that competitively inhibit the binding of angiotensin II to its receptor, resulting in blood vessel dilation and the reduction of blood pressure. These antagonists are also known as sartans, and are a group of pharmaceuticals that possess tetrazole or imidazole groups. In the present study, the anticancer and antimetastatic effects of the ARBs fimasartan, losartan, eprosartan and valsartan on the human prostate cancer PC-3, DU-145 and LNCap-LN3 cell lines were investigated in vitro...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28529316/pharmacological-modulation-of-autophagy-therapeutic-potential-and-persisting-obstacles
#5
REVIEW
Lorenzo Galluzzi, José Manuel Bravo-San Pedro, Beth Levine, Douglas R Green, Guido Kroemer
Autophagy is central to the maintenance of organismal homeostasis in both physiological and pathological situations. Accordingly, alterations in autophagy have been linked to clinically relevant conditions as diverse as cancer, neurodegeneration and cardiac disorders. Throughout the past decade, autophagy has attracted considerable attention as a target for the development of novel therapeutics. However, such efforts have not yet generated clinically viable interventions. In this Review, we discuss the therapeutic potential of autophagy modulators, analyse the obstacles that have limited their development and propose strategies that may unlock the full therapeutic potential of autophagy modulation in the clinic...
May 19, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28528980/phospholipase-c-%C3%AE-1-negatively-regulates-autophagy-in-colorectal-cancer-cells
#6
Makoto Shimozawa, Sakiho Anzai, Reiko Satow, Kiyoko Fukami
Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Kirsten rat sarcoma viral oncogene homolog (KRAS) is frequently mutated in CRC, and KRAS mutations promote cell motility, growth, and survival. We previously revealed that the expression of phospholipase C (PLC) δ1, one of the most basal PLCs, is down-regulated in colon adenocarcinoma, and that the KRAS signaling pathway suppresses PLCδ1 expression. Although recent studies revealed that KRAS mutations activate autophagy in cancer cells, a relation between PLCδ1 and autophagy remains unclear...
May 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28528979/sensitization-of-breast-cancer-cells-to-paclitaxel-by-dichloroacetate-through-inhibiting-autophagy
#7
Minghao Wang, Cuiwei Liao, Ying Hu, Wenqin Pan, Jun Jiang
Chemotherapy is still the main adjuvant strategy in the treatment of cancer, however, chemoresistance is also frequently encountered. Autophagy inhibition has been widely accepted as a promising therapeutic strategy in cancer, while the lack of effective and specific autophagy inhibitors hinders its application. Here we found that dichloroacetate (DCA), a small molecule compound, could significantly inhibit the autophagy induced by Doxorubicin in breast cancer cells. And DCA markedly enhances Doxorubicin-induced breast cancer cell death and anti-proliferation in vitro...
May 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28528977/imatinib-induces-autophagy-via-upregulating-xiap-in-gist882%C3%A2-cells
#8
Qingqing Xie, Qi Lin, Dezhi Li, Jianming Chen
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms originating from the gastrointestinal tract with gain of function mutations in receptor tyrosine kinases KIT or platelet-derived growth factor receptor A (PDGFRA). The main effective treatment for GISTs is tyrosine kinase inhibitors, such as imatinib mesylate. However, GISTs respond to imatinib treatment eventually develop acquired resistance, which is a main obstacle for GISTs therapy. Therefore, it's urgent to have a better understanding of the mechanisms underlying the imatinib resistance in GISTs to develop novel therapeutic strategies...
May 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28527723/activation-of-nrf2-signaling-augments-vesicular-stomatitis-virus-oncolysis-via-autophagy-driven-suppression-of-antiviral-immunity
#9
David Olagnier, Rassin R Lababidi, Samar Bel Hadj, Alexandre Sze, Yiliu Liu, Sharadha Dayalan Naidu, Matteo Ferrari, Yuan Jiang, Cindy Chiang, Vladimir Beljanski, Marie-Line Goulet, Elena V Knatko, Albena T Dinkova-Kostova, John Hiscott, Rongtuan Lin
Oncolytic viruses (OVs) offer a promising therapeutic approach to treat multiple types of cancer. In this study, we show that the manipulation of the antioxidant network via transcription factor Nrf2 augments vesicular stomatitis virus Δ51 (VSVΔ51) replication and sensitizes cancer cells to viral oncolysis. Activation of Nrf2 signaling by the antioxidant compound sulforaphane (SFN) leads to enhanced VSVΔ51 spread in OV-resistant cancer cells and improves the therapeutic outcome in different murine syngeneic and xenograft tumor models...
May 17, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
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
#10
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/28523294/autophagy-in-aging-and-disease
#11
Mădălina Fîlfan, Raluca Elena Sandu, Alexandra Daniela Zăvăleanu, Andrei GreşiŢă, Daniela Gabriela Glăvan, Denissa Greta Olaru, Aurel Popa-Wagner
Autophagy is a catabolic degradation system used to destroy and recycle the unnecessary or damaged components of a cell. Autophagy is present at a basal level in all mammals and is regulated by some conditions, such as oxidative stress, starvation or hypoxia. In aged tissues, increased but also decreased expression of autophagy-specific proteins, Beclin 1, LC3, Atg5 and Atg7 has been reported. Likewise, it could be shown that the lifespan of yeast, nematodes and flies is prolonged by pharmacologically stimulated autophagy using exogenous administered spermidine...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/28522753/cyclin-d1-restrains-oncogene-induced-autophagy-by-regulating-the-ampk-lkb1-signaling-axis
#12
Mathew C Casimiro, Gabriele Di Sante, Agnese Di Rocco, Emanuele Loro, Claudia Pupo, Tim Pestell, Sara Bisetto, Marco A Velasco-Velàzquez, Xuanmao Jiao, Zhiping Li, Christine M Kusminski, Erin L Seifert, Chenguang Wang, Daniel Ly, Bin Zheng, Che-Hung Shen, Philipp E Scherer, Richard G Pestell
Autophagy activated after DNA damage or other stresses mitigates cellular damage by removing damaged proteins, lipids and organelles. Activation of the master metabolic kinase AMPK enhances autophagy. Here we report that cyclin D1 restrains autophagy by modulating the activation of AMPK. In cell models of human breast cancer or in a cyclinD1-deficient model, we observed a cyclin D1-mediated reduction in AMPK activation. Mechanistic investigations showed that Cyclin D1 inhibited mitochondrial function, promoted glycolysis and reduced activation of AMPK (pT172), possibly through a mechanism that involves cyclin D1-Cdk4/Cdk6 phosphorylation of LKB1...
May 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28522553/glioblastoma-derived-cells-in-vitro-unveil-the-spectrum-of-drug-resistance-capabilty-comparative-study-of-tumour-chemosensitivity-in-different-culture-systems
#13
Monika Witusik-Perkowska, Magdalena Zakrzewska, Beata Sikorska, Wielislaw Papierz, Dariusz J Jaskolski, Janusz Szemraj, Pawel P Liberski
Resistance to cancer drugs is a complex phenomenon which could be influenced by in vitro conditions. However, tumour-derived cell cultures are routinely used for studies related to mechanisms of drug responsiveness or the search for new therapeutic approaches. The purpose of our work was to identify the potential differences in drug resistance and response to treatment of glioblastoma with the use of three in vitro models: traditional adherent culture, serum-free spheroid culture and novel adherent serum-free culture...
May 18, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28521459/cisplatin-regulates-cell-autophagy-in-endometrial-cancer-cells-via-the-pi3k-akt-mtor-signalling-pathway
#14
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/28518408/s-adenosylmethionine-mediated-apoptosis-is-potentiated-by-autophagy-inhibition-induced-by-chloroquine-in-human-breast-cancer-cells
#15
Donatella Delle Cave, Vincenzo Desiderio, Laura Mosca, Concetta Paola Ilisso, Luigi Mele, Michele Caraglia, Giovanna Cacciapuoti, Marina Porcelli
The naturally-occurring sulfonium compound S-adenosyl-L-methionine (AdoMet) is an ubiquitous sulfur-nucleoside that represents the main methyl donor in numerous methylation reactions. In recent years, it has been shown that AdoMet possesses antiproliferative properties in various cancer cells, but the molecular mechanisms at the basis of the effect induced by AdoMet have been only in part investigated. In the present study, we found that AdoMet strongly inhibited the proliferation of breast cancer cells MCF-7 by inducing both autophagy and apoptosis...
May 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28518150/cycloheximide-promotes-paraptosis-induced-by-inhibition-of-cyclophilins-in-glioblastoma-multiforme
#16
Lin Wang, Justin H Gundelach, Richard J Bram
Cancer is the second leading cause of death worldwide. Current treatment strategies based on multi-agent chemotherapy and/or radiation regimens have improved overall survival in some cases. However, resistance to apoptosis often develops in cancer cells, and its occurrence is thought to contribute to treatment failure. Non-apoptotic cell death mechanisms have become of great interest, therefore, in hopes that they would bypass tumor cell resistance. Glioblastoma multiforme (GBM), a grade IV astrocytic tumor is the most frequent brain tumor in adults, and has a high rate of mortality...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28516954/histone-deacetylase-10-structure-and-molecular-function-as-a-polyamine-deacetylase
#17
Yang Hai, Stephen A Shinsky, Nicholas J Porter, David W Christianson
Cationic polyamines such as spermidine and spermine are critical in all forms of life, as they regulate the function of biological macromolecules. Intracellular polyamine metabolism is regulated by reversible acetylation and dysregulated polyamine metabolism is associated with neoplastic diseases such as colon cancer, prostate cancer and neuroblastoma. Here we report that histone deacetylase 10 (HDAC10) is a robust polyamine deacetylase, using recombinant enzymes from Homo sapiens (human) and Danio rerio (zebrafish)...
May 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28516062/endoplasmic-reticulum-mitochondrial-ca-2-fluxes-underlying-cancer-cell-survival
#18
REVIEW
Hristina Ivanova, Martijn Kerkhofs, Rita M La Rovere, Geert Bultynck
Calcium ions (Ca(2+)) are crucial, ubiquitous, intracellular second messengers required for functional mitochondrial metabolism during uncontrolled proliferation of cancer cells. The mitochondria and the endoplasmic reticulum (ER) are connected via "mitochondria-associated ER membranes" (MAMs) where ER-mitochondria Ca(2+) transfer occurs, impacting the mitochondrial biology related to several aspects of cellular survival, autophagy, metabolism, cell death sensitivity, and metastasis, all cancer hallmarks. Cancer cells appear addicted to these constitutive ER-mitochondrial Ca(2+) fluxes for their survival, since they drive the tricarboxylic acid cycle and the production of mitochondrial substrates needed for nucleoside synthesis and proper cell cycle progression...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28515477/cancer-cachexia-associates-with-a-systemic-autophagy-inducing-activity-mimicked-by-cancer-cell-derived-il-6-trans-signaling
#19
Kristine Pettersen, Sonja Andersen, Simone Degen, Valentina Tadini, Joël Grosjean, Shinji Hatakeyama, Almaz N Tesfahun, Siver Moestue, Jana Kim, Unni Nonstad, Pål R Romundstad, Frank Skorpen, Sveinung Sørhaug, Tore Amundsen, Bjørn H Grønberg, Florian Strasser, Nathan Stephens, Dag Hoem, Anders Molven, Stein Kaasa, Kenneth Fearon, Carsten Jacobi, Geir Bjørkøy
The majority of cancer patients with advanced disease experience weight loss, including loss of lean body mass. Severe weight loss is characteristic for cancer cachexia, a condition that significantly impairs functional status and survival. The underlying causes of cachexia are incompletely understood, and currently no therapeutic approach can completely reverse the condition. Autophagy coordinates lysosomal destruction of cytosolic constituents and is systemically induced by starvation. We hypothesized that starvation-mimicking signaling compounds secreted from tumor cells may cause a systemic acceleration of autophagy during cachexia...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28515430/a-microfluidic-chip-for-screening-individual-cancer-cells-via-eavesdropping-on-autophagy-inducing-crosstalk-in-the-stroma-niche
#20
Hacer Ezgi Karakas, Junyoung Kim, Juhee Park, Jung Min Oh, Yongjun Choi, Devrim Gozuacik, Yoon-Kyoung Cho
Autophagy is a cellular homeostatic mechanism where proteins and organelles are digested and recycled to provide an alternative source of building blocks and energy to cells. The role of autophagy in cancer microenvironment is still poorly understood. Here, we present a microfluidic system allowing monitoring of the crosstalk between single cells. We used this system to study how tumor cells induced autophagy in the stromal niche. Firstly, we could confirm that transforming growth factor β1 (TGFβ1) secreted from breast tumor cells is a paracrine mediator of tumor-stroma interaction leading to the activation of autophagy in the stroma component fibroblasts...
May 17, 2017: Scientific Reports
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