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Autophagy and radiation resistance

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https://www.readbyqxmd.com/read/27911840/multistep-regulation-of-autophagy-by-wnk1
#1
Sachith Gallolu Kankanamalage, A-Young Lee, Chonlarat Wichaidit, Andres Lorente-Rodriguez, Akansha M Shah, Steve Stippec, Angelique W Whitehurst, Melanie H Cobb
The with-no-lysine (K) (WNK) kinases are an atypical family of protein kinases that regulate ion transport across cell membranes. Mutations that result in their overexpression cause hypertension-related disorders in humans. Of the four mammalian WNKs, only WNK1 is expressed throughout the body. We report that WNK1 inhibits autophagy, an intracellular degradation pathway implicated in several human diseases. Using small-interfering RNA-mediated WNK1 knockdown, we show autophagosome formation and autophagic flux are accelerated...
November 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27900012/ubenimex-enhances-the-radiosensitivity-of-renal-cell-carcinoma-cells-by-inducing-autophagic-cell-death
#2
Shuai Liu, Xiaoqing Wang, Jiaju Lu, Liping Han, Yongfei Zhang, Zheng Liu, Sentai Ding, Zhao Liu, Dongbin Bi, Zhihong Niu
Renal cell carcinoma (RCC) is resistant to standard radiotherapy. Ubenimex, an aminopeptidase N inhibitor, is widely used as an adjunct therapy after surgery to enhance the function of immunocompetent cells and confer antitumor effects. Our previous study demonstrated that ubenimex induces autophagic cell death in RCC cells. Recently, the molecular mechanism of autophagy induction has been associated with radiosensitivity in RCC cells. In the present study, the ability of ubenimex to enhance RCC cell sensitivity to radiation via the induction of autophagic cell death was determined, and the mechanism of action of this effect was investigated...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899501/unraveling-fungal-radiation-resistance-regulatory-networks-through-the-genome-wide-transcriptome-and-genetic-analyses-of-cryptococcus-neoformans
#3
Kwang-Woo Jung, Dong-Hoon Yang, Min-Kyu Kim, Ho Seong Seo, Sangyong Lim, Yong-Sun Bahn
The basidiomycetous fungus Cryptococcus neoformans has been known to be highly radiation resistant and has been found in fatal radioactive environments such as the damaged nuclear reactor at Chernobyl. To elucidate the mechanisms underlying the radiation resistance phenotype of C. neoformans, we identified genes affected by gamma radiation through genome-wide transcriptome analysis and characterized their functions. We found that genes involved in DNA damage repair systems were upregulated in response to gamma radiation...
November 29, 2016: MBio
https://www.readbyqxmd.com/read/27845767/activating-autophagy-to-potentiate-immunogenic-chemotherapy-and-radiation-therapy
#4
REVIEW
Lorenzo Galluzzi, José Manuel Bravo-San Pedro, Sandra Demaria, Silvia Chiara Formenti, Guido Kroemer
Autophagy is fundamental to the maintenance of intracellular homeostasis in virtually all human cells. Accordingly, defective autophagy predisposes healthy cells to undergoing malignant transformation. By contrast, malignant cells are able to harness autophagy to thrive, despite adverse microenvironmental conditions, and to resist therapeutic challenges. Thus, inhibition of autophagy has been proposed as a strategy to kill cancer cells or sensitize them to therapy; however, autophagy is also critical for optimal immune function, and mediates cell-extrinsic homeostatic effects owing to its central role in danger signalling by neoplastic cells responding to immunogenic chemotherapy and/or radiation therapy...
November 15, 2016: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/27845161/downregulation-of-autophagy-gene-expression-in-endometria-from-women-with-polycystic-ovary-syndrome
#5
Mirjana Sumarac-Dumanovic, Milica Apostolovic, Kristina Janjetovic, Danka Jeremic, Dusan Popadic, Aleksandar Ljubic, Jelena Micic, Jelena Dukanac-Stamenkovic, Aleksandra Tubic, Darko Stevanovic, Dragan Micic, Vladimir Trajkovic
Autophagy, a process of controlled cellular self-digestion, could be involved in cyclic remodeling of the human endometrium. We investigated endometrial mRNA expression of 23 autophagy-related (ATG) genes and transcription factors in healthy controls (n = 12) and anovulatory polycystic ovary syndrome (PCOS) patients (n = 24), as well as in their subgroup (n = 12) before and after metformin treatment. The mRNA levels of transcription factor forkhead box protein O1 (FOXO1) and several molecules involved in autophagosome formation (ATG13, RB1-inducible coiled-coil 1), autophagosome nucleation (ATG14, beclin 1, SH3-domain GRB2-like endophilin B1), autophagosome elongation (ATG3, ATG5, γ-aminobutyric acid receptor-associated protein - GABARAP), and delivery of ubiquitinated proteins to autophagosomes (sequestosome 1), were significantly reduced in anovulatory PCOS compared to healthy endometrium...
November 11, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27775833/targeting-deubiquitinating-enzymes-in-glioblastoma-multiforme-expectations-and-challenges
#6
Wei-Lin Jin, Xiao-Yuan Mao, Guan-Zhong Qiu
Glioblastoma (GBM) is regarded as the most common primary intracranial neoplasm. Despite standard treatment with tumor resection and radiochemotherapy, the outcome remains gloomy. It is evident that a combination of oncogenic gain of function and tumor-suppressive loss of function has been attributed to glioma initiation and progression. The ubiquitin-proteasome system is a well-orchestrated system that controls the fate of most proteins by striking a dynamic balance between ubiquitination and deubiquitination of substrates, having a profound influence on the modulation of oncoproteins, tumor suppressors, and cellular signaling pathways...
October 24, 2016: Medicinal Research Reviews
https://www.readbyqxmd.com/read/27757033/silver-nanoparticles-outperform-gold-nanoparticles-in-radiosensitizing-u251-cells-in-vitro-and-in-an-intracranial-mouse-model-of-glioma
#7
Peidang Liu, Haizhen Jin, Zhirui Guo, Jun Ma, Jing Zhao, Dongdong Li, Hao Wu, Ning Gu
Radiotherapy performs an important function in the treatment of cancer, but resistance of tumor cells to radiation still remains a serious concern. More research on more effective radiosensitizers is urgently needed to overcome such resistance and thereby improve the treatment outcome. The goal of this study was to evaluate and compare the radiosensitizing efficacies of gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) on glioma at clinically relevant megavoltage energies. Both AuNPs and AgNPs potentiated the in vitro and in vivo antiglioma effects of radiation...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27693581/fasting-boosts-sensitivity-of-human-skin-melanoma-to-cisplatin-induced-cell-death
#8
Fernanda Antunes, Marco Corazzari, Gustavo Pereira, Gian Maria Fimia, Mauro Piacentini, Soraya Smaili
Melanoma is one of leading cause of tumor death worldwide. Anti-cancer strategy includes combination of different chemo-therapeutic agents as well as radiation; however these treatments have limited efficacy and induce significant toxic effects on healthy cells. One of most promising novel therapeutic approach to cancer therapy is the combination of anti-cancer drugs with calorie restriction. Here we investigated the effect Cisplatin (CDDP), one of the most potent chemotherapeutic agent used to treat tumors, in association with fasting in wild type and mutated BRAF(V600E) melanoma cell lines...
September 29, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27507051/bh3-mimetic-obatoclax-gx15-070-mediates-mitochondrial-stress-predominantly-via-mcl-1-inhibition-and-induces-autophagy-dependent-necroptosis-in-human-oral-cancer-cells
#9
Prasad Sulkshane, Tanuja Teni
We have previously reported overexpression of antiapoptotic MCL-1 protein in human oral cancers and its association with therapy resistance and poor prognosis, implying it to be a potential therapeutic target. Hence, we investigated the efficacy and mechanism of action of Obatoclax, a BH3 mimetic pan BCL-2 inhibitor in human oral cancer cell lines. All cell lines exhibited high sensitivity to Obatoclax with complete clonogenic inhibition at 200-400 nM concentration which correlated with their MCL-1 expression...
August 5, 2016: Oncotarget
https://www.readbyqxmd.com/read/27478804/carcinoembryonic-antigen-expression-and-resistance-to-radiation-and-5-fluorouracil-induced-apoptosis-and-autophagy
#10
Ebrahim Eftekhar, Hajar Jaberie, Fakhraddin Naghibalhossaini
Understanding the mechanism of tumor resistance is critical for cancer therapy. In this study, we investigated the effect of carcinoembryonic antigen (CEA) overexpression on UV-and 5-fluorouracil (5-FU)-induced apoptosis and autophagy in colorectal cancer cells. We used histone deacetylase (HDAC) inhibitor, NaB and DNA demethylating agent, 5-azacytidine (5-AZA) to induce CEA expression in HT29/219 and SW742 colorectal cancer cell lines. MTT assay was used to measure IC50 value of the cells exposed to graded concentrations of 5- FU with either 0...
2016: International Journal of Molecular and Cellular Medicine
https://www.readbyqxmd.com/read/27414780/-nutrient-restriction-in-combinatory-therapy-of-tumors
#11
V V Senichkin, G S Kopeina, A V Zamaraev, I N Lavrik, B D Zhivotovsky
The main objective of anticancer treatment is the elimination of degenerated cells by the induction of programmed cell death. Various chemotherapy drugs and radiation are able to activate cell death mechanisms in tumors. However, unfortunately, monotherapy will always be insufficiently effective because of the variety and virulence of tumors, as well as their ability to develop resistance to drugs. Moreover, monotherapy might constrain many negative side effects. Therefore, the combination of different approaches and/or drugs will increase the efficiency of treatment...
May 2016: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/27380135/repression-of-the-autophagic-response-sensitises-lung-cancer-cells-to-radiation-and-chemotherapy
#12
Ilias V Karagounis, Dimitra Kalamida, Achilleas Mitrakas, Stamatia Pouliliou, Maria V Liousia, Alexandra Giatromanolaki, Michael I Koukourakis
BACKGROUND: The cellular autophagic response to radiation is complex. Various cells and tissues respond differentially to radiation, depending on both the dose of exposure and the time post irradiation. In the current study, we determined the autophagosomal and lysosomal response to radiation in lung cancer cell lines by evaluating the expression of the associated proteins, as well as the effect of relevant gene silencing in radio and chemosensitisation. Furthermore, tumour sensitisation was evaluated in in vivo autophagic gene silencing model after irradiation...
July 26, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27308528/an-expanded-role-for-mtorc1-in-autophagy
#13
Young-Mi Kim, Ji-Man Park, Douglas Grunwald, Do-Hyung Kim
Mechanistic target of rapamycin complex 1 (mTORC1) negatively regulates autophagy at early stages by phosphorylating Unc51-like kinase 1 (ULK1). Our recent study expanded the roles of mTORC1 in autophagy by identifying ultraviolet radiation resistance-associated gene product (UVRAG) as a substrate of mTORC1. This finding has provided new insight into the roles of mTORC1 in cellular membrane processes and cancer.
January 2016: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/27203177/autophagic-uvrag-promotes-uv-induced-photolesion-repair-by-activation-of-the-crl4-ddb2-e3-ligase
#14
Yongfei Yang, Shanshan He, Qiaoxiu Wang, Fan Li, Mi-Jeong Kwak, Sally Chen, Douglas O'Connell, Tian Zhang, Sara Dolatshahi Pirooz, YongHeui Jeon, Nyam-Osor Chimge, Baruch Frenkel, Younho Choi, Grace M Aldrovandi, Byung-Ha Oh, Zengqiang Yuan, Chengyu Liang
UV-induced DNA damage, a major risk factor for skin cancers, is primarily repaired by nucleotide excision repair (NER). UV radiation resistance-associated gene (UVRAG) is a tumor suppressor involved in autophagy. It was initially isolated as a cDNA partially complementing UV sensitivity in xeroderma pigmentosum (XP), but this was not explored further. Here we show that UVRAG plays an integral role in UV-induced DNA damage repair. It localizes to photolesions and associates with DDB1 to promote the assembly and activity of the DDB2-DDB1-Cul4A-Roc1 (CRL4(DDB2)) ubiquitin ligase complex, leading to efficient XPC recruitment and global genomic NER...
May 19, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27129175/enhanced-autophagy-in-colorectal-cancer-stem-cells-does-not-contribute-to-radio-resistance
#15
Chen Yan, Lan Luo, Shinji Goto, Yoshishige Urata, Chang-Ying Guo, Hanako Doi, Kaio Kitazato, Tao-Sheng Li
Autophagy, an essential catabolic pathway of degrading cellular components within the lysosome, has been found to benefit the growth and therapeutic resistance of cancer cells. In this study, we investigated the role of autophagy in the radio-sensitivity of cancer stem cells. By separating CD44+/CD133+ cancer stem cells from parental HCT8 human colorectal cancer cells, we found a significantly higher level of autophagy in the CD44+/CD133+ cells than in the parental cells. Exposure to 5 Gy of f-ray significantly damaged both CD44+/CD133+ cells and parental cells, but the radiation-induced damage did not differ between the groups...
April 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27109915/radiation-induced-autophagy-promotes-esophageal-squamous-cell-carcinoma-cell-survival-via-the-lkb1-pathway
#16
Chi Lu, Conghua Xie
Radiotherapy is an important treatment modality for esophageal cancer; however, the clinical efficacy of radiotherapy is limited by tumor radioresistance. In the present study, we explored the hypothesis that radiation induces tumor cell autophagy as a cytoprotective adaptive response, which depends on liver kinase B1 (LKB1) also known as serine/threonine kinase 11 (STK11). Radiation-induced Eca-109 cell autophagy was found to be dependent on signaling through the LKB1 pathway, and autophagy inhibitors that disrupted radiation-induced Eca-109 cell autophagy increased cell cycle arrest and cell death in vitro...
June 2016: Oncology Reports
https://www.readbyqxmd.com/read/27049248/prostate-cancer-cell-both-microrna-aberrant-expression-mediated-autophagy-and-radiation-therapy-resistance-with-short-cross-reference-to-epigenetic-genetic-mechanism-implications
#17
LETTER
C Alberti
No abstract text is available yet for this article.
2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27027348/tetrandrine-a-chinese-plant-derived-alkaloid-is-a-potential-candidate-for-cancer-chemotherapy
#18
Ting Liu, Xin Liu, Wenhua Li
Cancer is a disease caused by the abnormal proliferation and differentiation of cells governed by tumorigenic factors. Chemotherapy is one of the major cancer treatment strategies, and it functions by targeting the physiological capabilities of cancer cells, including sustained proliferation and angiogenesis, the evasion of programmed cell death, tissue invasion and metastasis. Remarkably, natural products have garnered increased attention in the chemotherapy drug discovery field because they are biologically friendly and have high therapeutic effects...
March 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/26993419/to-live-or-let-die-unclear-task-of-autophagy-in-the-radiosensitization-battle
#19
REVIEW
Martin Ondrej, Lucie Cechakova, Kamila Durisova, Jaroslav Pejchal, Ales Tichy
Radiation-induced autophagy is believed to represent a radioprotective mechanism of cancer cells. Thus, its inhibition should support radiation treatment and increase its efficacy. On the other hand, there is evidence that radiation alone or in combination with various chemical agents can induce autophagy that results into increased cell death, especially within transformed apoptosis-resistant cells. In this paper, besides description of autophagic process and its relation to cancer and radiotherapy, we compared two contradictory radiosensitization approaches that employ inhibition and induction of autophagy...
May 2016: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/26983466/a-role-for-abcg2-beyond-drug-transport-regulation-of-autophagy
#20
Rui Ding, Shengkan Jin, Kirk Pabon, Kathleen W Scotto
The ABC drug transporters, including ABCG2, are well known for their ability to efflux a wide spectrum of chemotherapeutic agents, thereby conferring a multidrug-resistant phenotype. However, studies over the past several years suggest that the ABC transporters may play additional role(s) in cell survival in the face of stress inducers that are not ABCG2 substrates (i.e., nutrient deprivation, ionizing radiation, rapamycin). The mechanism by which this occurs is largely unknown. In the present study, using several cancer cell lines and their ABCG2-overexpressing sublines, we show that cells overexpressing ABCG2 were more resistant to these stressors...
May 3, 2016: Autophagy
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