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Autophagy and cancer

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https://www.readbyqxmd.com/read/29677645/autophagy-as-a-cytoprotective-mechanism-in-esophageal-squamous-cell-carcinoma
#1
REVIEW
Timothy M Hall, Marie-Pier Tétreault, Kathryn E Hamilton, Kelly A Whelan
Esophageal squamous cell carcinoma (ESCC) is amongst the most aggressive human malignancies, representing a significant health burden worldwide. Autophagy is an evolutionarily conserved catabolic process that degrades and recycles damaged organelles and misfolded proteins to maintain cellular homeostasis. Alterations in autophagy are associated with cancer pathogenesis, including ESCC; however, the functional role of autophagy in ESCC remains elusive. Here, we discuss the clinical relevance of autophagy effectors in ESCC and review current knowledge regarding the molecular mechanisms through which autophagy contributes to ESCC...
April 17, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29676829/er-stress-mediated-autophagy-protects-against-%C3%AE-%C3%AE-dimethylacrylshikonin-induced-apoptosis-in-lung-adenocarcinoma-cells
#2
Haibing Wang, Gaochenxi Zhang
β,β-Dimethylacrylshikonin (DMAS) is an anti-cancer compound extracted from the roots of Lithospermum erythrorhizon. This study aims to investigate the effects of DMAS on human lung adenocarcinoma cells in vitro and explored the mechanisms of its anti-cancer action. We demonstrated that DMAS markedly inhibited cell viability in a dose- and time-dependent manner, and induced apoptosis as well as autophagy in human lung adenocarcinoma cells. Furthermore, we found that DMAS stimulated endoplasmic reticulum (ER) stress and mediated autophagy via the PERK-eIF2α-ATF4-CHOP and IRE1-TRAF2-JNK axises of the unfolded protein response (UPR) in human lung adenocarcinoma cells...
April 20, 2018: Cancer Science
https://www.readbyqxmd.com/read/29672851/human-hepatocellular-carcinoma-protection-by-melatonin
#3
REVIEW
Keywan Mortezaee
Despite great scientific breakthroughs toward understanding the identity of human hepatocellular carcinoma (HCC) mechanistically, there are still no clinically efficient therapeutic methods for this cancer. Melatonin (N-acetyl-5-methoxytryptamine) is a multi-tasking hormone that has long been known for its anti-cancer activity against various human cancers including HCC, which is a focus of this review. PubMed database was searched for relevant articles with the keywords: hepatocellular carcinoma (HCC), melatonin, apoptosis, proliferation, invasion, angiogenesis, autophagy, oxidative stress, tumor immunity, and mitogen-activated protein kinase (MAPK) focusing on just human cell lines and English language articles...
April 19, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29672318/a-novel-2-methoxyestradiol-analogue-is-responsible-for-vesicle-disruption-and-lysosome-aggregation-in-breast-cancer-cells
#4
Sandra D Nkandeu, Iman van den Bout, Marianne J Cronjé, Dirk H van Papendorp, Anna M Joubert
BACKGROUND: 2-Methoxyestradiol (2ME2) is an endogenous metabolite of 17-β-estradiol with anti-proliferative and anti-angiogenic properties. Due to 2ME2's rapid metabolism and low oral bioavailability in in vivo settings, 2ME2 analogues have been designed to alleviate these issues. One of these compounds is 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16). A previous work alluded to the ability of ESE-16 to induce autophagic cell death. Therefore, we investigated the mode of action of ESE-16 by studying its effects on autophagy, vesicle formation, and lysosomal organisation...
April 19, 2018: Pharmacology
https://www.readbyqxmd.com/read/29671878/targeting-autophagy-in-cancer
#5
REVIEW
Angelique V Onorati, Matheus Dyczynski, Rani Ojha, Ravi K Amaravadi
Autophagy is a conserved, self-degradation system that is critical for maintaining cellular homeostasis during stress conditions. Dysregulated autophagy has implications in health and disease. Specifically, in cancer, autophagy plays a dichotomous role by inhibiting tumor initiation but supporting tumor progression. Early results from clinical trials that repurposed hydroxychloroquine for cancer have suggested that autophagy inhibition may be a promising approach for advanced cancers. In this review of the literature, the authors present fundamental advances in the biology of autophagy, approaches to targeting autophagy, the preclinical rationale and clinical experience with hydroxychloroquine in cancer clinical trials, the potential role of autophagy in tumor immunity, and recent developments in next-generation autophagy inhibitors that have clinical potential...
April 19, 2018: Cancer
https://www.readbyqxmd.com/read/29670691/combined-acylselenourea-diselenide-structures-new-potent-and-selective-antitumoral-agents-as-autophagy-activators
#6
Pablo Garnica, Ignacio Encío, Daniel Plano, Juan A Palop, Carmen Sanmartín
A series of 16 new diselenide-acylselenourea conjugates have been designed following the fragment-based drug strategy. Compound in vitro cytotoxic potential was evaluated against six human cancer cell lines and two nonmalignant derived cell lines with the aim of determining their potency and selectivity. Nine derivatives exhibited GI50 values under 10 μM in at least four cancer cell lines. A clear gap situated phenyl substitution over heterocyclic moieties in terms of selectivity. Among carbocyclic compounds, derivatives 2 and 7 significantly inhibited cell growth of breast adenocarcinoma cells with GI50 values of 1...
April 12, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29670523/qianlie-xiaozheng-decoction-induces-autophagy-in-human-prostate-cancer-cells-via-inhibition-of-the-akt-mtor-pathway
#7
Yuehua Xu, Xueting Cai, Bin Zong, Rui Feng, Yali Ji, Gang Chen, Zhongxing Li
Qianlie Xiaozheng decoction (QLXZD), a traditional Chinese medicinal formula, has been used clinically to treat advanced prostate cancer (PCa) for more than 10 years. However, experimental evidence supporting its efficacy is lacking. Here, we investigated the anticancer properties and molecular mechanism of QLXZD in vitro in a human PCa cell line (PC3) and in vivo using PC3 xenografts in nude mice. We confirmed the antineoplastic activity of QLXZD by analyzing cell viability and tumor volume growth, which decreased significantly compared to that of the controls...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29670377/crocin-induces-autophagic-apoptosis-in-hepatocellular-carcinoma-by-inhibiting-akt-mtor-activity
#8
Chong Yao, Bing-Bing Liu, Xiao-Dong Qian, Li-Qin Li, Heng-Bin Cao, Qiao-Sheng Guo, Gui-Fen Zhou
Background: Autophagy induction is a common mechanism for antitumor chemicals in induction of cancer cell death. However, the role of autophagy in crocin-induced apoptosis is barely studied in hepatocellular carcinoma (HCC). Materials and methods: The influence of crocin on growth, apoptosis, and autophagy and its mutual relations were analyzed by Cell Counting Kit-8 assay, flow cytometer, EGFP-LC3 puncta analysis, and Western blot in HCC cells. The activities of Akt/mTOR axis and its roles in autophagy regulation were also detected by Western blot in HCC cells treated with crocin...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29670369/inhibition-of-nipbl-enhances-the-chemosensitivity-of-non-small-cell-lung-cancer-cells-via-the-dna-damage-response-and-autophagy-pathway
#9
Lei Zheng, Huanhuan Zhou, Liwei Guo, Xiaoling Xu, Shengjie Zhang, Weizhen Xu, Weimin Mao
Background: Previously, we reported that high expression of nipped-B-like protein (NIPBL) was strongly correlated with poor prognosis, tumor differentiation, and lymph node metastasis. Survival analysis indicated that NIPBL expression was a potential prognostic factor for non-small cell lung cancer (NSCLC). Moreover, loss of NIPBL decreased lung cancer cells proliferation, migration, invasion and promoted apoptosis as well as sensitivity to chemotherapeutic agents. However, the deep mechanisms were not explored...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29670359/d-limonene-exhibits-antitumor-activity-by-inducing-autophagy-and-apoptosis-in-lung-cancer
#10
Xiao Yu, Hongyan Lin, Yu Wang, Wenwen Lv, Shuo Zhang, Ying Qian, Xiaobei Deng, Nannan Feng, Herbert Yu, Biyun Qian
Purpose: d-limonene is a plant extract with widespread application, and it has been recently reported to have antiproliferative and proapoptotic effects on cancer cells. However, the mechanisms by which d-limonene achieves these effects, especially in lung cancer, are not entirely clear. Therefore, the goal of this study was to examine the effects of d-limonene on lung cancer and explore its mechanisms of action. Methods: We examined the therapeutic effects of d-limonene on lung cancer cells and in a xenograft animal model by characterizing its effects on the pathways of apoptosis and autophagy...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29669822/crosstalk-between-apoptosis-and-autophagy-is-regulated-by-the-arginylated-bip-beclin-1-p62-complex
#11
Yong J Lee, Xinxin Song, Dae-Hee Lee, Ashok-Kumar Dilly, Young-Sun Lee, Haroon Asif Choudry, Yong Tae Kwon, David L Bartlett
Emerging evidence demonstrates that autophagy and apoptosis are interconnected and their interplay greatly affects cell death. However, the key regulators in this crosstalk remain elusive. Therefore, the role of N-terminal arginylated BiP (R-BiP)/Beclin-1/p62 complex was examined in the crosstalk between apoptosis and autophagy during combination chemotherapy with mitomycin C and bortezomib using immunoblot, immunoprecipitation, and cellular imaging assays in wild-type and genetically engineered colorectal cancer cells...
April 18, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29669348/prazosin-but-not-tamsulosin-sensitises-pc-3-and-lncap-prostate-cancer-cells-to-docetaxel
#12
Briohny H Spencer, Catherine M McDermott, Russ Chess-Williams, David Christie, Shailendra Anoopkumar-Dukie
BACKGROUND/AIMS: Docetaxel is currently the first-line chemotherapeutic agent available for the treatment of patients with advanced prostate cancer (PCa). While docetaxel has been shown to modestly improve survival times for patients; they also experience significant docetaxel-induced toxicities. If treatment failure occurs, there are currently limited alternatives that show survival benefits for patients and therefore there is an urgent need for adjunct therapies. Some quinazoline-based alpha1-adrenoceptor (ADR) antagonists have previously been shown to have cytotoxic actions in PCa cells, but there is no research into their effects on docetaxel-induced toxicity...
April 17, 2018: Pharmacology
https://www.readbyqxmd.com/read/29667627/propofol-inhibits-hela-cells-by-impairing-autophagic-flux-via-amp-activated-protein-kinase-ampk-activation-and-endoplasmic-reticulum-stress-regulated-by-calcium
#13
Xi Chen, Kai Li, Guoqing Zhao
BACKGROUND Propofol has antitumor effects against various cancers. However, the mechanism of action of propofol in HeLa human cervical cancer cells has not been elucidated. MATERIAL AND METHODS We treated HeLa human cervical cancer cells with different concentrations of propofol. Cell viability was evaluated with Cell Counting Kit-8 and apoptosis was analyzed by annexin V-fluorescein isothiocyanate and propidium iodide staining and flow cytometry. Autophagosome formation was evaluated based on microtubule-associated protein light chain (LC)3 conversion and light chain 3 puncta formation...
April 18, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29667321/the-ethanol-extraction-of-prepared-psoralea-corylifolia-induces-apoptosis-and-autophagy-and-alteres-genes-expression-assayed-by-cdna-microarray-in-human-prostate-cancer-pc-3-cells
#14
Chia-Hsin Lin, Shinji Funayama, Shu-Fen Peng, Chao-Lin Kuo, Jing-Gung Chung
Prostate cancer is the most common male reproductive system cancer. The prevalence of prostate cancer in Europe and the United States is higher than that in the Asian region. However, the treatment of prostate cancer remains unsatisfactory. Psoralea corylifolia has been used to cure this disease as Chinese medicine in the Asian region. In this study, we analyzed the components of ethanol extraction of unprepared and prepared P. corylifolia by HPLC. Psoralen and isopsoralen content from the prepared P. corylifolia is twofold higher than that from unprepared, so we use the prepared extraction in this study...
April 18, 2018: Environmental Toxicology
https://www.readbyqxmd.com/read/29667105/the-role-of-autophagy-in-the-resistance-to-braf-inhibition-in-braf-mutated-melanoma
#15
Xiao Liu, Jinfeng Wu, Haihong Qin, Jinhua Xu
Malignant melanoma is the most aggressive and notorious skin cancer, and metastatic disease is associated with very poor long-term survival outcomes. Although metastatic melanoma patients with oncogenic mutations in the BRAF gene initially respond well to the treatment with specific BRAF inhibitors, most of them will eventually develop resistance to this targeted therapy. As a highly conserved catabolic process, autophagy is responsible for the maintenance of cellular homeostasis and cell survival, and is involved in multiple diseases, including cancer...
April 17, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29665051/hyperbaric-oxygen-treatment-sensitizes-gastric-cancer-cells-to-melatonin-induced-apoptosis-through-multiple-pathways
#16
Xiang Wei, Yinliang Qi, Ning Jia, Qing Zhou, Sumei Zhang, Yuan Wang
Although extensive efforts have been made in recent decades to treat advanced gastric cancer with comprehensive therapy based on chemotherapy, effective anti-gastric cancer therapeutics are still lacking in the clinics. Therefore, potent novel anti-gastric cancer ways are greatly needed. Here, we explored hyperbaric oxygen treatment as a novel and effective adjuvant treatment method which has anti-gastric cancer effects when used together with melatonin. When performed together with MLT, HBO effectively inhibited tumorigenicity of gastric cancer through selectively inducing a robust tumor suppressive apoptosis response...
April 17, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29665004/thiostrepton-degrades-mutant-p53-by-eliciting-an-autophagic-response-in-sw480-cells
#17
Dhanya Kalathil, Manu Prasad, Maharrish Chelladurai, Samu John, Asha S Nair
Mutations in p53 gene are one of the hallmarks of tumor development. Specific targeting of mutant p53 protein has a promising role in cancer therapeutics. Our preliminary observation showed destabilization of mutant p53 protein in SW480, MiaPaCa and MDAMB231 cell lines upon thiostrepton treatment. In order to elucidate the mechanism of thiostrepton triggered mutant p53 degradation, we explored the impact of proteasome inhibition on activation of autophagy. Combined treatment of thiostrepton and cycloheximide/chloroquine prevented the degradation of mutant p53 protein, reinforcing autophagy as the means of mutant p53 destabilization...
April 17, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29663416/autophagy-induction-by-trehalose-molecular-mechanisms-and-therapeutic-impacts
#18
REVIEW
Kiana Hosseinpour-Moghaddam, Michele Caraglia, Amirhossein Sahebkar
The balance between synthesis and degradation is crucial to maintain cellular homeostasis and different mechanisms are known to keep this balance. In this review, we will provide a short overview on autophagy as an intracellular homeostatic degradative machinery. We will also describe the involvement of downregulation of autophagy in numerous diseases including neurodegenerative diseases, cancer, aging, metabolic disorders, and other infectious diseases. Therefore, modulation of autophagic processes can represent a promising way of intervention in different diseases including neurodegeneration and cancer...
April 16, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29663364/impact-of-iaspp-on-chemoresistance-through-plk1-and-autophagy-in-ovarian-clear-cell-carcinoma
#19
Ka-Kui Chan, Oscar Gee-Wan Wong, Esther Shuk-Ying Wong, Karen Kar-Loen Chan, Philip Pun-Ching Ip, Ka-Yu Tse, Annie Nga-Yin Cheung
Ovarian clear cell carcinoma (OCCC) is a type of epithelial ovarian cancer that is strongly associated with endometriosis, resistance against conventional chemotherapy and thus poorer prognosis. The expression of inhibitory member of the ASPP family proteins (iASPP) and Polo-like kinase (PLK)1 were significantly higher in OCCC compared to benign cystadenomas and endometriosis. Both protein expressions were found to correlate with chemoresistance in patients with OCCC while high iASPP expression alone was significantly associated with a poor patient survival...
April 16, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29662615/transcriptome-and-proteome-profiling-reveals-stress-induced-expression-signatures-of-imiquimod-treated-tasmanian-devil-facial-tumor-disease-dftd-cells
#20
Amanda L Patchett, Richard Wilson, Jac C Charlesworth, Lynn M Corcoran, Anthony T Papenfuss, Bruce A Lyons, Gregory M Woods, Cesar Tovar
As a topical cancer immunotherapy, the toll-like receptor 7 ligand imiquimod activates tumor regression via stimulation of immune cell infiltration and cytotoxic responses. Imiquimod also exerts direct pro-apoptotic effects on tumor cells in vitro , but a role for these effects in imiquimod-induced tumor regression remains undefined. We previously demonstrated that cell lines derived from devil facial tumor disease (DFTD), a transmissible cancer threatening the survival of the Tasmanian devil ( Sarcophilus harrisii ), are sensitive to imiquimod-induced apoptosis...
March 23, 2018: Oncotarget
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