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Autophagy and cancer

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https://www.readbyqxmd.com/read/28646136/recurrent-background-mutations-in-whi2-impair-proteostasis-and-degradation-of-misfolded-cytosolic-proteins-in-saccharomyces-cerevisiae
#1
Sophie A Comyn, Stéphane Flibotte, Thibault Mayor
Proteostasis promotes viability at both the cellular and organism levels by maintaining a functional proteome. This requires an intricate protein quality control (PQC) network that mediates protein folding by molecular chaperones and removes terminally misfolded proteins via the ubiquitin proteasome system and autophagy. How changes within the PQC network can perturb proteostasis and shift the balance between protein folding and proteolysis remain poorly understood. However, given that proteostasis is altered in a number of conditions such as cancer and ageing, it is critical that we identify the factors that mediate PQC and understand the interplay between members of the proteostatic network...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28644842/investigation-of-discriminant-metabolites-in-tamoxifen-resistant-and-choline-kinase-alpha-downregulated-breast-cancer-cells-using-1h-nuclear-magnetic-resonance-spectroscopy
#2
Hoe Suk Kim, Lianji Tian, Hyeonjin Kim, Woo Kyung Moon
Metabolites linked to changes in choline kinase-α (CK-α) expression and drug resistance, which contribute to survival and autophagy mechanisms, are attractive targets for breast cancer therapies. We previously reported that autophagy played a causative role in driving tamoxifen (TAM) resistance of breast cancer cells (BCCs) and was also promoted by CK-α knockdown, resulting in the survival of TAM-resistant BCCs. There is no comparative study yet about the metabolites resulting from BCCs with TAM-resistance and CK-α knockdown...
2017: PloS One
https://www.readbyqxmd.com/read/28644386/capsaicin-induces-autophagy-and-apoptosis-in-human-nasopharyngeal-carcinoma-cells-by-downregulating-the-pi3k-akt-mtor-pathway
#3
Yu-Tsai Lin, Hung-Chen Wang, Yi-Chiang Hsu, Chung-Lung Cho, Ming-Yu Yang, Chih-Yen Chien
Capsaicin is a potential chemotherapeutic agent for different human cancers. In Southeast China, nasopharyngeal carcinoma (NPC) has the highest incidence of all cancers, but final treatment outcomes are unsatisfactory. However, there is a lack of information regarding the anticancer activity of capsaicin in NPC cells, and its effects on the signaling transduction pathways related to apoptosis and autophagy remain unclear. In the present study, the precise mechanisms by which capsaicin exerts anti-proliferative effects, cell cycle arrest, autophagy and apoptosis were investigated in NPC-TW01 cells...
June 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28642840/cytolethal-distending-toxin-enhances-radiosensitivity-in-prostate-cancer-cells-by-regulating-autophagy
#4
Hwai-Jeng Lin, Hsin-Ho Liu, Chia-Der Lin, Min-Chuan Kao, Yu-An Chen, Chuan Chiang-Ni, Zhi-Pei Jiang, Mei-Zi Huang, Chun-Jung Lin, U-Ging Lo, Li-Chiung Lin, Cheng-Kuo Lai, Ho Lin, Jer-Tsong Hsieh, Cheng-Hsun Chiu, Chih-Ho Lai
Cytolethal distending toxin (CDT) produced by Campylobacter jejuni contains three subunits: CdtA, CdtB, and CdtC. Among these three toxin subunits, CdtB is the toxic moiety of CDT with DNase I activity, resulting in DNA double-strand breaks (DSB) and, consequently, cell cycle arrest at the G2/M stage and apoptosis. Radiation therapy is an effective modality for the treatment of localized prostate cancer (PCa). However, patients often develop radioresistance. Owing to its particular biochemical properties, we previously employed CdtB as a therapeutic agent for sensitizing radioresistant PCa cells to ionizing radiation (IR)...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28642707/tetrandrine-an-activator-of-autophagy-induces-autophagic-cell-death-via-pkc-%C3%AE-inhibition-and-mtor-dependent-mechanisms
#5
Vincent Kam Wai Wong, Wu Zeng, Juan Chen, Xiao Jun Yao, Elaine Lai Han Leung, Qian Qian Wang, Pauline Chiu, Ben C B Ko, Betty Yuen Kwan Law
Emerging evidence suggests the therapeutic role of autophagic modulators in cancer therapy. This study aims to identify novel traditional Chinese medicinal herbs as potential anti-tumor agents through autophagic induction, which finally lead to autophagy mediated-cell death in apoptosis-resistant cancer cells. Using bioactivity-guided purification, we identified tetrandrine (Tet) from herbal plant, Radix stephaniae tetrandrae, as an inducer of autophagy. Across a number of cancer cell lines, we found that breast cancer cells treated with tetrandrine show an increase autophagic flux and formation of autophagosomes...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28642035/improving-the-efficacy-of-hormone-therapy-in-breast-cancer-the-role-ofcholesterol-metabolism-in-serm-mediated-autophagy-cell-differentiation-and-death
#6
REVIEW
Julie Leignadier, Florence Dalenc, Marc Poirot, Sandrine Silvente-Poirot
Breast cancer (BC) is one of the most common female cancers in the world, with estrogen receptor (ER)-positive BC the most frequent subtype. Tamoxifen (Tam) is an effective drug that competitively binds to the ER and is routinely used for the treatment of ER-positive BC. However, a number of ER-positive BC do not respond to Tam treatment and acquired resistance is often observed, constituting a major challenge for extending patient life expectancy. The mechanisms responsible for these treatment failures remain unclear, indicating the requirement for other targets and better predictors for patient response to Tam...
June 19, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28639909/silencing-of-nrage-induces-autophagy-via-ampk-ulk1-atg13-signaling-pathway-in-nsclc-cells
#7
Yiyang Zhou, Nan Huang, Jianchun Wu, Ni Zhen, Ning Li, Yan Li, Yong-Xin Li
NRAGE has been reported to be overexpressed in cancer cells, especially in lung cancer cells. To determine the role of NRAGE in non-small-cell lung cancer cells, we investigated the effects of NRAGE on autophagy in non-small-cell lung cancer cells. Human A549 and H1299 cells were transfected with NRAGE-specific small-interfering RNA. The Cell Counting Kit-8 and plate clone assay showed that downregulation of NRAGE could induce the proliferation in A549 and H1299 cells. In addition, our data suggested that downregulation of NRAGE enhances autophagosome formation by immunofluorescence...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28639902/mild-hyperthermia-enhances-sensitivity-of-gastric-cancer-cells-to-chemotherapy-through-reactive-oxygen-species-induced-autophagic-death
#8
Ming-Chen Ba, Hui Long, Shu-Zhong Cui, Yuan-Feng Gong, Zhao-Fei Yan, Shuai Wang, Yin-Bing Wu
Mild hyperthermia enhances anti-cancer effects of chemotherapy, but the precise biochemical mechanisms involved are not clear. This study was carried out to investigate whether mild hyperthermia sensitizes gastric cancer cells to chemotherapy through reactive oxygen species-induced autophagic death. In total, 20 BABL/c mice of MKN-45 human gastric cancer tumor model were divided into hyperthermia + chemotherapy group, hyperthermia group, chemotherapy group, N-acetyl-L-cysteine group, and mock group. Reactive oxygen species production and expression of autophagy-related genes Beclin1, LC3B, and mammalian target of rapamycin were determined...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28638475/tamoxifen-activates-nrf2-dependent-sqstm1-transcription-to-promote-endometrial-hyperplasia
#9
Lifeng Feng, Jiaqiu Li, Lixian Yang, Libo Zhu, Xiufeng Huang, Shuzheng Zhang, Likang Luo, Zhinong Jiang, Tingting Jiang, Wenxia Xu, Xian Wang, Hongchuan Jin
Long-term application of Tamoxifen (TAM) is usually recommended for hormone receptor positive breast cancer patients. Unfortunately, TAM will inevitably increase the incidence of endometrial hyperplasia even endometrial cancer. Despite of substantial investigations, no effective approaches to prevent TAM-induced endometrial carcinogenesis have been acknowledged. In this study, we found that inhibition of Nrf2 could be valuable to prevent TAM-induced endometrial hyperplasia. Upon TAM treatment, the mRNA and protein expression of autophagy adaptor SQSTM1 was specifically increased in endometrial cells but not breast cancer cells...
2017: Theranostics
https://www.readbyqxmd.com/read/28637020/autophagy-related-genes-are-induced-by-histone-deacetylase-inhibitor-suberoylanilide-hydroxamic-acid-via-the-activation-of-cathepsin-b-in-human-breast-cancer-cells
#10
Han Han, Jing Li, Xiuyan Feng, Hui Zhou, Shanchun Guo, Weiqiang Zhou
Autophagy is involved in modulating tumor cell motility and invasion, resistance to epithelial-to-mesenchymal transition, anoikis, and escape from immune surveillance. We have previous shown that SAHA is capable to induce several apoptosis and autophagy-related gene expression in breast cancers. However, the exact mechanisms of autophagy activation in this context have not been fully identified. Our results showed that the expression and the activity of Cathepsin B (CTSB), one of the major lysosomal cysteine proteases, were significantly increased in MDA-MB- 231 and MCF-7 cells upon SAHA treatment...
June 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28637004/autophagy-is-required-for-crizotinib-induced-apoptosis-in-met-amplified-gastric-cancer-cells
#11
Rebecca D Schroeder, Woonyoung Choi, David S Hong, David J McConkey
MET amplification has been clinically credentialed as a therapeutic target in gastric cancer, but the molecular mechanisms underlying sensitivity and resistance to MET inhibitors are still not well understood. Using whole-genome mRNA expression profiling, we identified autophagy as a top molecular pathway that was activated by the MET inhibitor crizotinib in drug-sensitive human gastric cancer cells, and functional studies confirmed that crizotinib increased autophagy levels in the drug-sensitive cells in a concentration-dependent manner...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28635401/inhibition-of-long-non-coding-rna-ror-reverses-resistance-to-tamoxifen-by-inducing-autophagy-in-breast-cancer
#12
Yuehua Li, Baohong Jiang, Hongbo Zhu, Xiaofei Qu, Liqin Zhao, Yeru Tan, Yiling Jiang, Mingchu Liao, Xiaoping Wu
This study explored the mechanism underlying long non-coding RNA ROR regulating autophagy on Tamoxifen resistance in breast cancer. Cancer tissues and adjacent normal tissues were collected from 74 breast cancer patients. Human breast cancer BT474 cells were assigned into blank, phosphate buffered saline, Tamoxifen, negative control + Tamoxifen, siROR + Tamoxifen, 3-methyladenine + Tamoxifen, and siROR + 3-methyladenine + TA groups. The expression of long non-coding RNA ROR and expressions of multi-drug resistance-associated P-glycoprotein and glutathione S-transferase-π messenger RNA were detected using quantitative real-time polymerase chain reaction...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28635397/induction-of-apoptosis-and-autophagy-by-calcifying-nanoparticles-in-human-bladder-cancer-cells
#13
Ji-Hua Wu, Yao-Liang Deng, Quan Liu, Jun-Chuan Yu, Yun-Long Liu, Zi-Qi He, Xiao-Feng Guan
Calcifying nanoparticles have been linked to various types of human disease, but how they contribute to disease processes is unclear. Here, we examined whether and how calcifying nanoparticles isolated from patients with kidney stones are cytotoxic to human bladder cancer cells. Calcifying nanoparticles were isolated from midstream urine of patients with renal calcium oxalate stones and examined by electron microscopy. Human bladder cancer cells (EJ cells) were cultured in the presence of calcifying nanoparticles or nanohydroxyapatites for 12 and 72 h and examined for toxicity using the Cell Counting Kit-8, for autophagy using transmission electron microscopy and confocal microscopy, and for apoptosis using fluorescence microscopy, transmission electron microscopy, and flow cytometry...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28635310/how-can-tricyclic-sophoridinic-derivatives-be-used-as-autophagy-inhibitors-for-cancer-treatments
#14
Yan Xiang Wang, Zhan Dong Liu, Chong Wen Bi, Lu Liu, Hong Bin Deng, Dan Qing Song
No abstract text is available yet for this article.
June 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28631572/endoplasmic-reticulum-stress-could-induce-autophagy-and-apoptosis-and-enhance-chemotherapy-sensitivity-in-human-esophageal-cancer-ec9706-cells-by-mediating-pi3k-akt-mtor-signaling-pathway
#15
Fang Zhou, Yan-Hua Li, Jian-Jun Wang, Jia Pan, Hong Lu
The study was designed to explore the mechanism of tunicamycin-induced endoplasmic reticulum stress in human esophageal cancer EC9706 cells and EC109 cells, as well as its effects on cell autophagy, apoptosis, and chemoresistance. Tunicamycin-induced endoplasmic reticulum stress model was established in EC9706 and EC109 cell lines. Western blotting was employed to detect the expression of endoplasmic reticulum stress iconic protein GRP78. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to evaluate the effect of different cisplatin and tunicamycin concentrations on survival rate of EC9706 cells and EC109 cells...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28630390/kavalactone-yangonin-induces-autophagy-and-sensitizes-bladder-cancer-cells-to-flavokawain-a-and-docetaxel-via-inhibition-of-the-mtor-pathway
#16
Liu Zhongbo, Ha U-Syn, Yu Ke, Wu Chunli, Yokoyama Noriko, Zi Xiaolin
Consumption of kava (Piper methysticum Forst) has been linked to reduced cancer risk in the South Pacific Islands. Kavalactones are major bioactive components in kava root extracts, which have recently demonstrated anti-cancer activities. However, molecular mechanisms of kavalactones' anti-cancer action remain largely unknown. We have identified two kavalactones, yangonin and 5' 6'-dehydrokawain, as potent inducers of autophagic cell death in bladder cancer cells. The effect of yangonin inducing autophagy is associated with increased expression of beclin and ATG5...
June 20, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28629173/autophagic-mechanism-in-anti-cancer-immunity-its-pros-and-cons-for-cancer-therapy
#17
REVIEW
Ying-Ying Li, Lynn G Feun, Angkana Thongkum, Chiao-Hui Tu, Shu-Mei Chen, Medhi Wangpaichitr, Chunjing Wu, Macus T Kuo, Niramol Savaraj
Autophagy, a self-eating machinery, has been reported as an adaptive response to maintain metabolic homeostasis when cancer cells encounter stress. It has been appreciated that autophagy acts as a double-edge sword to decide the fate of cancer cells upon stress factors, molecular subtypes, and microenvironmental conditions. Currently, the majority of evidence support that autophagy in cancer cells is a vital mechanism bringing on resistance to current and prospective treatments, yet whether autophagy affects the anticancer immune response remains unclear and controversial...
June 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28628644/targeting-multiple-pro-apoptotic-signaling-pathways-with-curcumin-in-prostate-cancer-cells
#18
Mariela Rivera, Yanilda Ramos, Madeline Rodríguez-Valentín, Sheila López-Acevedo, Luis A Cubano, Jin Zou, Qiang Zhang, Guangdi Wang, Nawal M Boukli
Curcumin, an extract from the turmeric rhizome (Curcuma longa), is known to exhibit anti-inflammatory, antioxidant, chemopreventive and antitumoral activities against aggressive and recurrent cancers. Accumulative data indicate that curcumin may induce cancer cell death. However, the detailed mechanism underlying its pro-apoptotic and anti-cancer effects remains to be elucidated. In the present study, we examined the signaling pathways triggered by curcumin, specifically, the exact molecular mechanisms of curcumin-induced apoptosis in highly metastatic human prostate cancer cells...
2017: PloS One
https://www.readbyqxmd.com/read/28628188/silencing-of-bag3-promotes-the-sensitivity-of-ovarian-cancer-cells-to-cisplatin-via-inhibition-of-autophagy
#19
Shuang Qiu, Liang Sun, Ye Jin, Qi An, Changjiang Weng, Jianhua Zheng
Ovarian cancer is the most lethal disease among all gynecological malignancies. Interval cytoreductive surgery and cisplatin‑based chemotherapy are the recommended therapeutic strategies. However, acquired resistance to cisplatin remains a big challenge for the overall survival and prognosis in ovarian cancer. Complicated molecular mechanisms are involved in the process. At present, increasing evidence indicates that autophagy plays an important role in the prosurvival and resistance against chemotherapy...
July 2017: Oncology Reports
https://www.readbyqxmd.com/read/28628113/microrna-20a-mediated-loss-of-autophagy-contributes-to-breast-tumorigenesis-by-promoting-genomic-damage-and-instability
#20
L Liu, J He, X Wei, G Wan, Y Lao, W Xu, Z Li, H Hu, Z Hu, X Luo, J Wu, W Xie, Y Zhang, N Xu
Gene expression analysis of The Cancer Genome Atlas (TCGA) breast cancer data set show that miR-20a is upregulated in human breast cancer, especially in triple-negative subtype. Gene Set Enrichment Analysis suggests that miR-20a expression negatively correlates with the autophagy/lysosome pathway. We report here that miR-20a inhibits the basal and nutrient starvation-induced autophagic flux and lysosomal proteolytic activity, increases intracellular reactive oxygen species levels and DNA damage response by targeting several key regulators of autophagy, including BECN1, ATG16L1 and SQSTM1...
June 19, 2017: Oncogene
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