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Autophagy and apoptosis and radiotherapy

Xiaogang Zheng, Xiaodong Jin, Feifei Li, Xiongxiong Liu, Yan Liu, Fei Ye, Ping Li, Ting Zhao, Qiang Li
Energetic carbon ions (CI) offer great advantages over conventional radiations such as X- or γ-rays in cancer radiotherapy. High linear energy transfer (LET) CI can induce both endoplasmic reticulum (ER) stress and autophagy in tumor cells under certain circumstances. The molecular connection between ER stress and autophagy in tumor exposed to high-LET radiation and how these two pathways influence the therapeutic effect against tumor remain poorly understood. In this work, we studied the impact of autophagy and apoptosis induced by ER stress following high-LET CI radiation on the radiosensitivity of S180 cells both in vitro and in vivo...
February 2017: Medical Oncology
Marta Denel-Bobrowska, Agnieszka Marczak
Survivin is a member of the family of apoptosis inhibitors. It regulates several essential cellular processes, i.e. it inhibits apoptosis and promotes cell proliferation, DNA repair and autophagy. Survivin is responsible for development of the cell's resistance to chemotherapy and radiotherapy. Overexpression of survivin generally correlates with poor prognosis. Its presence has been detected in most types of human tumours. Currently much attention is paid to the possibilities of using this protein as a diagnostic marker of cancer or a prognostic factor...
December 8, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
Ya-Guang Li, Nai-Xin Liang, Ying-Zhi Qin, Dong-Jie Ma, Chang-Jin Huang, Lei Liu, Shan-Qing Li
This study examined the effects of RNAi-mediated TUSC3 silencing on radiation-induced autophagy and radiation sensitivity of human lung adenocarcinoma cell line A549 under hypoxic condition. Different CoCl2 concentrations were used to treat A549 cells and establish a CoCl2-induced hypoxic model of A549 cells. MTT and clone formation assays were used to determine the effects of different concentrations of CoCl2 on the growth and proliferation of A549 cells treated by different doses of X-ray irradiation. The siRNA-expressing vector was transfected by liposomes and for silencing of TUSC3...
November 30, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Mingsheng Zhang, Enda Xue, Wei Shao
BACKGROUND: Nephroblastoma (Wilms' tumor [WT]) is the most common malignant renal cancer in children. Although the outcome of WT has significantly improved as a result of the combination of surgery, chemotherapy, and radiotherapy; in some cases WT results in severe complications. Thus, novel strategies that would decrease treatment burden are required. The aim of the current study was to investigate the synergistic antitumor effect of andrographolide (AND) in combination with vincristine (VCR) on WT cells...
2016: Drug Design, Development and Therapy
Jingli Hao, Peter Graham, Lei Chang, Jie Ni, Valerie Wasinger, Julia Beretov, Junli Deng, Wei Duan, Joseph Bucci, David Malouf, David Gillatt, Yong Li
Radioresistance is a major challenge for prostate cancer (CaP) metastasis and recurrence after radiotherapy. This study aimed to identify potential protein markers and signaling pathways associated with radioresistance using a PC-3 radioresistant (RR) subcutaneous xenograft mouse model and verify the radiosensitization effect from a selected potential candidate. PC-3RR and PC-3 xenograft tumors were established and differential protein expression profiles from two groups of xenografts were analyzed using liquid chromatography tandem-mass spectrometry...
September 30, 2016: Oncotarget
Zhiyang Wang, Shuai Liu, Kejia Ding, Sentai Ding, Chensheng Li, Jiaju Lu, Dexuan Gao, Tong Zhang, Dongbin Bi
Renal cell carcinoma (RCC) accounts for 3 % of all adult malignancies and is the most lethal urological cancer. Livin is a member of the inhibitor of apoptosis protein (IAP) family, which is associated with tumor resistance to radiotherapy and chemotherapy. Clinical data also showed that patients with high tumor grades and stages have higher expression levels of Livin in RCC cells. Autophagy is a survival mechanism activated in response to nutrient deprivation. A possible role of Livin in the autophagy of RCC cells has not been investigated; therefore, this pioneer study was carried out...
November 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Hongxing Ye, Mantao Chen, Fei Cao, Hongguang Huang, Renya Zhan, Xiujue Zheng
BACKGROUND: Glioblastoma is refractory to conventional treatment, which is combined of surgery, chemotherapy and radiotherapy. Recent studies have shown that glioma initiating cells (GICs) contribute to tumorigenesis and radioresistance. Recently, other studies showed that the GICs use the autophagy as the major pathway to survive. Chloroquine, an anti-malarial chemical, is an autophagic inhibitor which blocks autophagosome fusion with lysosome and slows down lysosomal acidification. The aim of this study was to explore the mechanisms of chloroquine on the radiosensitivity of GICs...
September 20, 2016: BMC Neurology
Wei Guo, Yu Wang, Zhu Wang, Yan-Ping Wang, Hong Zheng
Chemotherapy, radiotherapy, and endocrinotherapy are documented to induce autophagy among breast cancer cells, but the role of autophagy in this disease has been attributed as cytoprotective as well as tumor-suppressing. Thus we studied MDA-MB-231 and SK-BR-3 breast cancer cell lines treated with epirubicin (EPI) to assess autophagy and apoptosis. We found out that EPI induced apoptosis and autophagy in both cell lines. The lysosomal inhibitor bafilomycin A1 inhibited cellular autophagy and enhanced EPI-triggered apoptosis, perhaps due to inhibition of autolysosome formation, which then inhibited autophagic effects of engulfing and clearing damaged mitochondria...
November 2016: Cancer Science
Hao Wu, Jun Lin, Peidang Liu, Zhihai Huang, Peng Zhao, Haizhen Jin, Jun Ma, Longping Wen, Ning Gu
Malignant glioma is one of the most common intracranial tumor with a dismal prognosis. The radiosensitizing effect of silver nanoparticles (AgNPs) on glioma both in vitro and in vivo were demonstrated in the previous studies of our group. However, the underlying mechanism is still unclear. In this present study, the use of antioxidants is employed for the regulating of reactive oxygen species (ROS) in U251 cells treated with various agents, and the results shows that ROS played an essential role in the autophagy inducing and radiosensitization effect of AgNPs...
September 2016: Biomaterials
Xiaoli Li, Yanyan Cen, Yongqing Cai, Tao Liu, Huan Liu, Guanqun Cao, Dan Liu, Bin Li, Wei Peng, Jintao Zou, Xueli Pang, Jiang Zheng, Hong Zhou
Synthetic oligodeoxynucleotides containing unmethylated CpG dinucleotides (CpG ODN) function as potential radiosensitizers for glioma treatment, although the underlying mechanism is unclear. It was observed that CpG ODN107, when combined with irradiation, did not induce apoptosis. Herein, the effect of CpG ODN107 + irradiation on autophagy and the related signaling pathways was investigated. In vitro, CpG ODN107 + irradiation induced autophagosome formation, increased the ratio of LC3 II/LC3 I, beclin 1 and decreased p62 expression in U87 cells...
2016: Scientific Reports
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
Xiangyu Liu, Kangjian Sun, Handong Wang, Yuyuan Dai
Glioblastoma multiforme (GBM) is one of the deadliest forms of cancer due to its limited sensitivity to chemotherapy and radiotherapy. Cisplatin (CCDP) is a widely used chemotherapeutic agent for tumors, but the agent often results in the development of chemo-resistance. In several cancers, cisplatin resistance is associated with autophagy induction. Here, we found that in glioma cells cisplatin treatment induced autophagy. Our data indicates that the autophagy induction plays a critical role in cisplatin resistance of glioma cells, knockdown of RB inhibited autophagy induced by cisplatin, and inhibition of autophagy improved cisplatin-induced apoptosis...
May 4, 2016: Neuroscience Letters
Chih-Chia Yu, Hsien-bin Huang, Shih-Kai Hung, Hui-Fen Liao, Ching-Chih Lee, Hon-Yi Lin, Szu-Chin Li, Hsu-Chueh Ho, Chung-Lin Hung, Yu-Chieh Su
BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most common malignant neoplasms in Taiwan. Activation of the mTOR signaling pathway has been linked to decreased radiation responsiveness in human oral cancer, thus it limits efficacy of radiotherapy. To address this question, we investigated the effect of AZD2014, a novel small molecular ATP-competitive inhibitor of mTORC1 and mTORC2 kinase, as a radiosensitizer in primary OSCC and OSCC-derived cell line models. METHODS: We isolated primary tumor cells from OSCC tissues and cell lines...
2016: PloS One
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
Moureq Alotaibi, Khushboo Sharma, Tareq Saleh, Lawrence F Povirk, Eric A Hendrickson, David A Gewirtz
Radiotherapy continues to be a primary modality in the treatment of cancer. In addition to promoting apoptosis, radiation-induced DNA damage can promote autophagy and senescence, both of which can theoretically function to prolong tumor survival. In this work, we tested the hypothesis that autophagy and/or senescence could be permissive for DNA repair, thereby facilitating tumor cell recovery from radiation-induced growth arrest and/or cell death. In addition, studies were designed to elucidate the involvement of autophagy and senescence in radiosensitization by PARP inhibitors and the re-emergence of a proliferating tumor cell population...
March 2016: Radiation Research
Yanzhou Yang, Hoi Hung Cheung, Wai Nok Law, Cheng Zhang, Wai Yee Chan, Xiuying Pei, Yanrong Wang
Ovarian cryopreservation by vitrification is a highly useful method for preserving female fertility during radiotherapy and chemotherapy. However, cryoinjury, osmotic stress during vitrification, and ischemia/reperfusion during transplantation lead to loss of ovarian follicles. Ovarian follicle loss may be partially reduced by several methods; however, studies regarding the mechanism of ovarian follicle loss have only investigated cell apoptosis, which consists of type I programmed cell death. Autophagy is type II programmed cell death, and cell homeostasis is maintained by autophagy during conditions of stress...
June 2016: Biology of Reproduction
Monika Paul-Samojedny, Adam Pudełko, Małgorzata Kowalczyk, Anna Fila-Daniłow, Renata Suchanek-Raif, Paulina Borkowska, Jan Kowalski
BACKGROUND: Glioblastoma multiforme (GBM) is the most malignant and invasive human brain tumor, and it is characterized by a poor prognosis and short survival time. Current treatment strategies for GBM, using surgery, chemotherapy and/or radiotherapy, are ineffective. The PI3K/AKT/PTEN signaling pathway is frequently deregulated in this cancer, and it is connected with regulation of the cell cycle, apoptosis, and autophagy. OBJECTIVES: The current study was undertaken to examine the effect of small interfering RNA (siRNA) targeting the AKT3 and PIK3CA genes on the susceptibility of T98G cells to temozolomide (TMZ) and carmustine (BCNU)...
April 2016: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
Nina Stojcheva, Gennadi Schechtmann, Steffen Sass, Patrick Roth, Ana-Maria Florea, Anja Stefanski, Kai Stühler, Marietta Wolter, Nikola S Müller, Fabian J Theis, Michael Weller, Guido Reifenberger, Caroline Happold
Glioblastoma is the most aggressive brain tumor in adults with a median survival below 12 months in population-based studies. The main reason for tumor recurrence and progression is constitutive or acquired resistance to the standard of care of surgical resection followed by radiotherapy with concomitant and adjuvant temozolomide (TMZ/RT→TMZ). Here, we investigated the role of microRNA (miRNA) alterations as mediators of alkylator resistance in glioblastoma cells. Using microarray-based miRNA expression profiling of parental and TMZ-resistant cultures of three human glioma cell lines, we identified a set of differentially expressed miRNA candidates...
March 15, 2016: Oncotarget
Lele Song, Linyan Ma, Gende Chen, Yingying Huang, Xiaojin Sun, Chenchen Jiang, Hao Liu
OBJECTIVE: To explore the effects of 3-methyladenine (3-MA, an autophagy inhibitor) on sensitivities of nasopharyngeal carcinoma cells to radiotherapy and chemotherapy and the underlying mechanisms.
 METHODS: Cell proliferation was examined by MTT and colony formation assay, while cell apoptosis was evaluated by annexin V/PI double staining and 2-(4-Amidinophenyl)-6-indolecarbamidine dihydrochloride (DAPI) staining. Mitochondrial membrane potential was measured by commercial kit (JC-1)...
January 2016: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
Long Wang, Linmei Long, Wenjuan Wang, Zhongqin Liang
Glioblastoma is a malignant human cancer that confers a dismal prognosis. Ionizing radiation (IR) is applied as the standard treatment for malignant gliomas. However, radiotherapy remains merely palliative because of the existence of glioma stem cells (GSCs), which are regarded as highly radioresistant "seed" cells. In this study, the effect and possible mechanisms of radiotherapy in combination with resveratrol (Res) were investigated in a radioresistant GSC line, SU-2. Our results showed that Res inhibited SU-2 proliferation and enhanced radiosensitivity as indicated by clonogenic survival assay...
December 2015: Journal of Pharmacological Sciences
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