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autophagy and IR and cancer

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https://www.readbyqxmd.com/read/29679028/radiosensitization-by-marine-sponge-agelas-sp-extracts-in-hepatocellular-carcinoma-cells-with-autophagy-induction
#1
Changhoon Choi, Arang Son, Hyi-Seung Lee, Yeon-Ju Lee, Hee Chul Park
Although radiation therapy is an effective treatment modality in many cancers, there is an urgent need to develop therapeutic drugs capable of overcoming radioresistance or minimizing normal tissue toxicity. A wide variety of marine-derived bioactive compounds have been screened for anti-cancer drug discovery, but little is known regarding radiation therapy applications. In this study, six different extracts of marine sponges collected from the Micronesian sea were screened for anti-cancer and radiosensitizing activity...
April 20, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29656200/photoinduced-anticancer-activity-studies-of-iridium-iii-complexes-targeting-mitochondria-and-tubules
#2
Wen-Yao Zhang, Qian-Yan Yi, Yang-Jie Wang, Fan Du, Miao He, Bing Tang, Dan Wan, Yun-Jun Liu, Hong-Liang Huang
Three new iridium (III) complexes [Ir (ppy)2 (ipbc)](PF6 ) (1), [Ir (bzq)2 (ipbc)](PF6 ) (2) and [Ir (piq)2 (ipbc)](PF6 ) (3) were designed and synthesized. All the complexes were tested for anticancer activity using 3-(4,5-dimethylthiazole)-2,5-diphenyltetraazolium bromide (MTT) method. The complexes show no cytotoxic activity toward cancer BEL-7402, SGC-7901, Eca-109, A549, HeLa and HepG2 cells. However, upon irradiation with white light, the complexes display high cytotoxicity against BEL-7402 cells with an IC50 value of 5...
April 7, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29620258/autophagy-inhibition-enhances-radiosensitivity-of-eca%C3%A2-109-cells-via-the-mitochondrial-apoptosis-pathway
#3
Hua Tao, Pudong Qian, Jincheng Lu, Yesong Guo, Huanfeng Zhu, Feijiang Wang
Autophagy inhibition is crucial for the improvement of the efficacy of radiotherapy in cancer. The aim of the present study was to determine the potential therapeutic value of autophagy and its correlation with mitochondria in human esophageal carcinoma cells following treatment with ionizing radiation (IR). Autophagy in Eca‑109 cells was induced under poor nutrient conditions. The formation of autophagic vacuoles was monitored using electron microscopy. In addition, cell apoptosis after IR and mitochondrial membrane potential (MMP) were analyzed by flow cytometry...
March 29, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29610318/ablation-of-insulin-receptor-substrates-1-and-2-suppresses-kras-driven-lung-tumorigenesis
#4
He Xu, Min-Sik Lee, Pei-Yun Tsai, Ashley S Adler, Natasha L Curry, Saketh Challa, Elizaveta Freinkman, Daniel S Hitchcock, Kyle D Copps, Morris F White, Roderick T Bronson, Michael Marcotrigiano, Yaotang Wu, Clary B Clish, Nada Y Kalaany
Non-small-cell lung cancer (NSCLC) is a leading cause of cancer death worldwide, with 25% of cases harboring oncogenic Kirsten rat sarcoma ( KRAS ). Although KRAS direct binding to and activation of PI3K is required for KRAS -driven lung tumorigenesis, the contribution of insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R) in the context of mutant KRAS remains controversial. Here, we provide genetic evidence that lung-specific dual ablation of insulin receptor substrates 1/2 ( Irs1 / Irs2 ), which mediate insulin and IGF1 signaling, strongly suppresses tumor initiation and dramatically extends the survival of a mouse model of lung cancer with Kras activation and p53 loss...
April 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29459645/inhibition-of-atg12-mediated-autophagy-by-mir-214-enhances-radiosensitivity-in-colorectal-cancer
#5
J L Hu, G Y He, X L Lan, Z C Zeng, J Guan, Y Ding, X L Qian, W T Liao, Y Q Ding, L Liang
Radioresistance hampers success in the treatment of patients with advanced colorectal cancer (CRC). Improving our understanding of the underlying mechanisms of radioresistance could increase patients' response to irradiation (IR). MicroRNAs are a class of small RNAs involved in tumor therapy response to radiation. Here we found that miR-214 was markedly decreased in CRC cell lines and blood of CRC patients after IR exposure. Meanwhile, autophagy was enhanced in irradiated CRC cells. Mechanically, ATG12 was predicted and identified as a direct target of miR-214 by dual luciferase assay, qPCR, and Western blot...
February 20, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29393406/deoxycytidine-kinase-participates-in-the-regulation-of-radiation-induced-autophagy-and-apoptosis-in-breast-cancer-cells
#6
Rui Zhong, Bing Liang, Rui Xin, Xuanji Zhu, Zhuo Liu, Qiao Chen, Yufei Hou, Zhao Jin, Mu Qi, Shumei Ma, Xiaodong Liu
Deoxycytidine kinase (dCK) is a rate limiting enzyme critical for the phosphorylation of endogenous deoxynucleosides and for the anti‑tumor activity of many nucleoside analogs. dCK is activated in response to ionizing radiation (IR) and it is required for the G2/M checkpoint induced by IR. However, whether dCK plays a role in radiation-induced autophagy and apoptosis is less clear. In this study, we reported that dCK decreased IR-induced total cell death and apoptosis, and increased IR-induced autophagy in SKBR3 and MDA‑MB‑231 breast cancer cell lines...
January 22, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29331805/synthesis-characterization-and-anticancer-activity-in-vitro-and-in-vivo-evaluation-of-an-iridium-iii-polypyridyl-complex
#7
Qiao-Yan Yi, Dan Wan, Bing Tang, Yang-Jie Wang, Wen-Yao Zhang, Fan Du, Miao He, Yun-Jun Liu
An iridium (III) complex [Ir(ppy)2 (BDPIP)]PF6 (Ir-1) was reported to show high anticancer activity and may be used as a potent anticancer drug. In the current study, we designed and synthesized a novel iridium (III) complex and evaluated its potential inhibitory effect on the cancer cell growth in vitro and in vivo. This complex was found to display high cytotoxic activity in vitro and in vivo against A549 cell with a low IC50 value of 3.6 ± 0.3 μM and inhibiting percentage of tumor growth is 63...
February 10, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29331753/an-iridium-iii-complex-as-potent-anticancer-agent-induces-apoptosis-and-autophagy-in-b16-cells-through-inhibition-of-the-akt-mtor-pathway
#8
Bing Tang, Dan Wan, Yang-Jie Wang, Qiao-Yan Yi, Bo-Hong Guo, Yun-Jun Liu
A new ligand THPDP (THPDP = 11-(6,7,8,9-tetrahydrophenazin-2-yl)dipyrido[3,2-a:2',3'-c]phenazine) and its iridium(III) complex [Ir(ppy)2 (THPDP)]PF6 (Ir-1) was synthesized and characterized by elemental analysis, IR, ESI-MS, 1 H NMR and 13 C NMR. The cytotoxicity in vitro of the complex against cancer cells B16, A549, Eca-109, SGC-7901, BEL-7402 and normal NIH 3T3 cell lines was evaluated using MTT method. The IC50 values of the complex toward B16, A549 and Eca-109 cells are 1.0 ± 0.02, 1.4 ± 0...
February 10, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29321496/genistein-promotes-ionizing-radiation-induced-cell-death-by-reducing-cytoplasmic-bcl-xl-levels-in-non-small-cell-lung-cancer
#9
Zhimin Zhang, Feng Jin, Xiaojuan Lian, Mengxia Li, Ge Wang, Baohua Lan, Hao He, Guo-Dong Liu, Yan Wu, Guiyin Sun, Cheng-Xiong Xu, Zhen-Zhou Yang
Genistein (GEN) has been previously reported to enhance the radiosensitivity of cancer cells; however, the detailed mechanisms remain unclear. Here, we report that GEN treatment inhibits the cytoplasmic distribution of Bcl-xL and increases nuclear Bcl-xL in non-small cell lung cancer (NSCLC). Interestingly, our in vitro data show that ionizing radiation IR treatment significantly increases IR-induced DNA damage and apoptosis in a low cytoplasmic Bcl-xL NSCLC cell line compared to that of high cytoplasmic Bcl-xL cell lines...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29069798/efficient-cell-death-induction-in-human-glioblastoma-cells-by-photodynamic-treatment-with-tetrahydroporphyrin-tetratosylat-thpts-and-ionizing-irradiation
#10
Peter Hambsch, Yury P Istomin, Dimitri A Tzerkovsky, Ina Patties, Jochen Neuhaus, Rolf-Dieter Kortmann, Stanislav Schastak, Annegret Glasow
BACKGROUND: So far, glioblastomas cannot be cured by standard therapy and have an extremely poor median survival of about 15 months. The photodynamic therapy (PDT) with next generation photosensitizers, reaching a higher therapeutic depth, might offer a new, adjuvant treatment strategy in brain cancer therapy. Here, we investigated the effect of THPTS-PDT combined with ionizing irradiation (IR) on glioblastoma cells in vitro and in vivo . RESULTS: THPTS colocalized to mitochondria and was not found in the nucleus...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050670/ginseng-polysaccharide-serves-as-a-potential-radiosensitizer-through-inducing-apoptosis-and-autophagy-in-the-treatment-of-osteosarcoma
#11
Xiao-Yu Zhang, Ke Sun, Qi Zhu, Tao Song, Yang Liu
Recent studies have confirmed that the combined use of anti-cancer drugs with ionizing radiation (IR) could improve the sensitivity of osteosarcoma (OS) cells. Therefore, it is necessary to identify potential effective drugs for the enhancement of IR-radiosensitivity. In the current study, we found that 20, 10, 5, and 1 μM of ginseng polysaccharide (GPS) significantly suppressed MG-63 cell viability with or without γ-ray radiation in a dose- and time-dependent manner. Strikingly, 20 μM of GPS combined with 5 Gy treatment suppressed colony formation capacity by nearly 13...
November 2017: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/28837154/akt2-suppresses-pro-survival-autophagy-triggered-by-dna-double-strand-breaks-in-colorectal-cancer-cells
#12
Nina Seiwert, Carina Neitzel, Svenja Stroh, Teresa Frisan, Marc Audebert, Mahmoud Toulany, Bernd Kaina, Jörg Fahrer
DNA double-strand breaks (DSBs) are critical DNA lesions, which threaten genome stability and cell survival. DSBs are directly induced by ionizing radiation (IR) and radiomimetic agents, including the cytolethal distending toxin (CDT). This bacterial genotoxin harbors a unique DNase-I-like endonuclease activity. Here we studied the role of DSBs induced by CDT and IR as a trigger of autophagy, which is a cellular degradation process involved in cell homeostasis, genome protection and cancer. The regulatory mechanisms of DSB-induced autophagy were analyzed, focusing on the ATM-p53-mediated DNA damage response and AKT signaling in colorectal cancer cells...
August 24, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28642840/cytolethal-distending-toxin-enhances-radiosensitivity-in-prostate-cancer-cells-by-regulating-autophagy
#13
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/28627629/reducing-autophagy-and-inducing-g1-phase-arrest-by-aloperine-enhances-radio-sensitivity-in-lung-cancer-cells
#14
Zhijie Xu, Yuanliang Yan, Shuangshuang Zeng, Long Qian, Shuang Dai, Lingfang Xiao, Lin Wang, Xue Yang, Yi Xiao, Zhicheng Gong
Aloperine (ALO), an isolated alkaloid from the leaves of Sophora alopecuroides (S. alopecuroides), has been suggested to exhibit anti-inflammatory and antitumor properties, and has been traditionally used to treat various diseases, including cancers. However, little is known about the effects of ALO on the radio-sensitivity of lung cancer cells. In the present study, we confirmed that agent ALO inhibits cell growth, promotes cell aopotosis and induces G1 phase arrest and consequently enhanced the radio-sensitivity in radio-resistant lung cancer cells A549/IR...
June 19, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28585811/dinuclear-ru-ii-bipy-2-derivatives-structural-biological-and-in-vivo-zebrafish-toxicity-evaluation
#15
Oscar A Lenis-Rojas, Catarina Roma-Rodrigues, Alexandra R Fernandes, Fernanda Marques, David Pérez-Fernández, Jorge Guerra-Varela, Laura Sánchez, Digna Vázquez-García, Margarita López-Torres, Alberto Fernández, Jesús J Fernández
Ruthenium-based drugs exhibit interesting properties as potential anticancer pharmaceuticals. We herein present the synthesis and characterization of a new family of ruthenium complexes with formulas [{Ru(bipy)2 }2 (μ-L)][CF3 SO3 ]4 (L = bptz, 1a) and [{Ru(bipy)2 }2 (μ-L)][CF3 SO3 ]2 (L = arphos, 2a; dppb, 3a; dppf, 4a), which were synthesized from the Ru(II) precursor compound cis-Ru(bipy)2 Cl2 . The complexes were characterized by elemental analysis, mass spectrometry,1 H and31 P{1 H} NMR, IR spectroscopy, and conductivity measurements...
June 19, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28212561/the-tlr7-agonist-imiquimod-induces-anti-cancer-effects-via-autophagic-cell-death-and-enhances-anti-tumoral-and-systemic-immunity-during-radiotherapy-for-melanoma
#16
Jeong Hyun Cho, Hyo-Ji Lee, Hyun-Jeong Ko, Byung-Il Yoon, Jongseon Choe, Keun-Cheol Kim, Tae-Wook Hahn, Jeong A Han, Sun Shim Choi, Young Mee Jung, Kee-Ho Lee, Yun-Sil Lee, Yu-Jin Jung
Toll-like receptor (TLR) ligands are strongly considered immune-adjuvants for cancer immunotherapy and have been shown to exert direct anti-cancer effects. This study was performed to evaluate the synergistic anti-cancer and anti-metastatic effects of the TLR7 agonist imiquimod (IMQ) during radiotherapy for melanoma. The pretreatment of B16F10 or B16F1 cells with IMQ combined with γ-ionizing radiation (IR) led to enhanced cell death via autophagy, as demonstrated by increased expression levels of autophagy-related genes, and an increased number of autophagosomes in both cell lines...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28147244/the-pi3k-inhibitor-gdc-0941-enhances-radiosensitization-and-reduces-chemoresistance-to-temozolomide-in-gbm-cell-lines
#17
Fei Shi, Hongchuan Guo, Rong Zhang, Hongyu Liu, Liangliang Wu, Qiyan Wu, Jialin Liu, Tianyi Liu, Qiuhang Zhang
Glioblastoma multiforme (GBM) is among the most lethal of all human tumors. It is the most frequently occurring malignant primary brain tumor in adults. The current standard of care (SOC) for GBM is initial surgical resection followed by treatment with a combination of temozolomide (TMZ) and ionizing radiation (IR). However, GBM has a dismal prognosis, and survivors have compromised quality of life owing to the adverse effects of radiation. GBM is characterized by overt activity of the phosphoinositide 3-kinase (PI3K) signaling pathway...
March 27, 2017: Neuroscience
https://www.readbyqxmd.com/read/27958338/ester-modified-cyclometalated-iridium-iii-complexes-as-mitochondria-targeting-anticancer-agents
#18
Fang-Xin Wang, Mu-He Chen, Xiao-Ying Hu, Rui-Rong Ye, Cai-Ping Tan, Liang-Nian Ji, Zong-Wan Mao
Organometallic iridium complexes are potent anticancer candidates which act through different mechanisms from cisplatin-based chemotherapy regimens. Here, ten phosphorescent cyclometalated iridium(III) complexes containing 2,2'-bipyridine-4,4'-dicarboxylic acid and its diester derivatives as ligands are designed and synthesized. The modification by ester group, which can be hydrolysed by esterase, facilitates the adjustment of drug-like properties. The quantum yields and emission lifetimes are influenced by variation of the ester substituents on the Ir(III) complexes...
December 13, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27849558/identification-of-a-fluorescent-small-molecule-enhancer-for-therapeutic-autophagy-in-colorectal-cancer-by-targeting-mitochondrial-protein-translocase-tim44
#19
Yinghui Huang, Jie Zhou, Shenglin Luo, Yang Wang, Jintao He, Peng Luo, Zelin Chen, Tao Liu, Xu Tan, Juanjuan Ou, Hongming Miao, Houjie Liang, Chunmeng Shi
OBJECTIVE: As the modulation of autophagic processes can be therapeutically beneficial to cancer treatment, the identification of novel autophagic enhancers is highly anticipated. However, current autophagy-inducing anticancer agents exert undesired side effects owing to their non-specific biodistribution in off-target tissues. This study aims to develop a multifunctional agent to integrate cancer targeting, imaging and therapy and to investigate its mechanism. DESIGN: A series of mitochondria-targeting near-infrared (NIR) fluorophores were synthesised, screened and identified for their autophagy-enhancing activity...
February 2018: Gut
https://www.readbyqxmd.com/read/27711766/cyclometallated-iridium-complexes-inducing-paraptotic-cell-death-like-natural-products-synthesis-structure-and-mechanistic-aspects
#20
Suman Kumar Tripathy, Umasankar De, Niranjan Dehury, Paltan Laha, Manas Kumar Panda, Hyung Sik Kim, Srikanta Patra
Six mononuclear Ir complexes (1-6) using polypyridyl-pyrazine based ligands (L1 and L2) and {[cp*IrCl(μ-Cl)]2 and [(ppy)2 Ir(μ-Cl)]2 } precursors have been synthesised and characterised. Complexes 1-5 have shown potent anticancer activity against various human cancer cell lines (MCF-7, LNCap, Ishikawa, DU145, PC3 and SKOV3) while complex 6 is found to be inactive. Flow cytometry studies have established that cellular accumulation of the complexes lies in the order 2 > 1 > 5 > 4 > 3 > 6 which is in accordance with their observed cytotoxicity...
September 27, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
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