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Autophagy and radioresistance

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https://www.readbyqxmd.com/read/27793904/pulsed-electromagnetic-field-with-temozolomide-can-elicit-an-epigenetic-pro-apoptotic-effect-on-glioblastoma-t98g-cells
#1
Francesca Pasi, Lorenzo Fassina, Maria Evelina Mognaschi, Giuseppe Lupo, Franco Corbella, Rosanna Nano, Enrica Capelli
Treatment with pulsed electromagnetic fields (PEMFs) is emerging as an interesting therapeutic option for patients with cancer. The literature has demonstrated that low-frequency/low-energy electromagnetic fields do not cause predictable effects on DNA; however, they can epigenetically act on gene expression. The aim of the present work was to study a possible epigenetic effect of a PEMF, mediated by miRNAs, on a human glioblastoma cell line (T98G). We tested a PEMF (maximum magnetic induction, 2 mT; frequency, 75 Hz) that has been demonstrated to induce autophagy in glioblastoma cells...
November 2016: Anticancer Research
https://www.readbyqxmd.com/read/27708237/proteomic-identification-of-the-lactate-dehydrogenase-a-in-a-radioresistant-prostate-cancer-xenograft-mouse-model-for-improving-radiotherapy
#2
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
https://www.readbyqxmd.com/read/27694690/suppression-of-pc-1-prlz-sensitizes-prostate-cancer-cells-to-ionizing-radiation-by-attenuating-dna-damage-repair-and-inducing-autophagic-cell-death
#3
Zeng-Fu Shang, Qiang Wei, Lan Yu, Fang Huang, Bei-Bei Xiao, Hongtao Wang, Man Song, Li Wang, Jianguang Zhou, Jian Wang, Shanhu Li
Radiotherapy is promising and effective for treating prostate cancer but the addition of a tumor cell radiosensitizer would improve therapeutic outcomes. PC-1/PrLZ, a TPD52 protein family member is frequently upregulated in advanced prostate cancer cells and may be a biomarker of aggressive prostate cancer. Therefore, we investigated the potential role of PC-1/PrLZ for increasing radioresistance in human prostate cancer cell lines. Growth curves and survival assays after g-ray irradiation confirmed that depletion of endogenous PC-1/PrLZ significantly increased prostate cancer cell radiosensitivity...
September 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27644442/chloroquine-an-autophagy-inhibitor-potentiates-the-radiosensitivity-of-glioma-initiating-cells-by-inhibiting-autophagy-and-activating-apoptosis
#4
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
https://www.readbyqxmd.com/read/27626497/artesunate-enhances-the-therapeutic-response-of-glioma-cells-to-temozolomide-by-inhibition-of-homologous-recombination-and-senescence
#5
Nancy Berte, Stefanie Lokan, Marcus Eich, Ella Kim, Bernd Kaina
Glioblastoma multiforme (GBM), a malignant brain tumor with a dismal prognosis, shows a high level of chemo- and radioresistance and, therefore, attempts to sensitize glioma cells are highly desired. Here, we addressed the question of whether artesunate (ART), a drug currently used in the treatment of malaria, enhances the killing response of glioblastoma cells to temozolomide (TMZ), which is the first-line therapeutic for GBM. We measured apoptosis, necrosis, autophagy and senescence, and the extent of DNA damage in glioblastoma cells...
September 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27335774/hypoxia-induced-autophagy-as-an-additional-mechanism-in-human-osteosarcoma-radioresistance
#6
Helin Feng, Jin Wang, Wei Chen, Baoen Shan, Yin Guo, Jianfa Xu, Ling Wang, Peng Guo, Yingze Zhang
Osteosarcoma (OS) responds poorly to radiotherapy, but the mechanism is unclear. We found OS tumor tissues expressed high level of protein HIF-1α, a common biological marker indicative of hypoxia. It is known that hypoxic cells are generally radioresistant because of reduced production of irradiation-induced DNA-damaging reactive oxygen species (ROS) in the anaerobic condition. Here we report another mechanism how hypoxia induces radioresistance. In MG-63 human osteosarcoma cells, hypoxic pretreatment increased the cellular survival in irradiation...
June 2016: Journal of Bone Oncology
https://www.readbyqxmd.com/read/27327120/hypoxia-responsive-mir-301a-and-mir-301b-promote-radioresistance-of-prostate-cancer-cells-via-downregulating-ndrg2
#7
Wei Wang, Mingbo Liu, Yawei Guan, Qingwu Wu
BACKGROUND MiR-301a and miR-301b are 2 oncomiRs involved in multiple types of cancer. In this study, we explored the expression change of miR-301a and miR-301b in prostate cancer cells in hypoxia and studied their regulation of autophagy and radiosensitivity of prostate cancer cells. MATERIAL AND METHODS QRT-PCR was performed to quantify the expression change of miR-301a and miR-301b in hypoxia. Their effects on autophagy were measured by Western blot analysis, and their effects on radiosensitivity were measured by clonogenic assay and flow cytometry...
2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27220494/mir-21-modulates-radiosensitivity-of-cervical-cancer-through-inhibiting-autophagy-via-the-pten-akt-hif-1%C3%AE-feedback-loop-and-the-akt-mtor-signaling-pathway
#8
Lili Song, Shikai Liu, Liang Zhang, Hairong Yao, Fangyuan Gao, Dongkui Xu, Qian Li
MiR-21 is an important microRNA (miRNA) modulating radiosensitivity of cervical cancer cells. However, the underlying mechanism of miR-21 upregulation in radioresistant cervical cancer has not been fully understood. In addition, autophagy may either promote or alleviate radioresistance, depending on the types of cancer and tumor microenvironment. How autophagy affects radiosensitivity in cervical cancer and how miR-21 is involved in this process has not been reported. This study showed that miR-21 upregulation in radioresistant cervical cancer is related to HIF-1α overexpression...
May 25, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27199567/stathmin1-increases-radioresistance-by-enhancing-autophagy-in-non-small-cell-lung-cancer-cells
#9
Xi Zhang, Jingfen Ji, Yu Yang, Juan Zhang, Liangfang Shen
Radioresistance has been demonstrated to be involved in the poor prognosis of patients with non-small-cell lung cancer (NSCLC). However, the underlying mechanism remains largely unclear. Investigation on special therapeutic targets associated with radioresistance shows promises for the enhancement of clinical radiotherapy effect toward NSCLC. This study aimed to reveal the role of Stathmin1 (STMN1) in radioresistance in NSCLC as well as the underlying mechanism. Our data showed that the protein levels of STMN1 were significantly upregulated in NSCLC cells subjected to radiation, accompanied with the activation of autophagy...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27135967/different-roles-of-chop-and-jnk-in-mediating-radiation-induced-autophagy-and-apoptosis-in-breast-cancer-cells
#10
Feifei Li, Xiaogang Zheng, Yan Liu, Ping Li, Xiongxiong Liu, Fei Ye, Ting Zhao, Qingfeng Wu, Xiaodong Jin, Qiang Li
Unfolded protein response (UPR) is comprised of complex and conserved stress pathways that function as a short-term adaptive mechanism to reduce levels of unfolded or misfolded proteins and maintain homeostasis in the endoplasmic reticulum (ER). UPR can be triggered by prolonged or persistent ER stress under many physiological or pathological conditions, including radiation exposure. Radiation-induced ER stress elicits autophagy and apoptosis in cancer cells, where C/EBP homologous protein (CHOP) and c-Jun NH2-terminal kinase (JNK) may play crucial roles...
May 2016: Radiation Research
https://www.readbyqxmd.com/read/27109915/radiation-induced-autophagy-promotes-esophageal-squamous-cell-carcinoma-cell-survival-via-the-lkb1-pathway
#11
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/27026538/the-impact-of-autophagy-on-cell-death-modalities-in-crl-5876-lung-adenocarcinoma-cells-after-their-exposure-to-%C3%AE-rays-and-or-erlotinib
#12
Otilija Keta, Tanja Bulat, Igor Golić, Sebastien Incerti, Aleksandra Korać, Ivan Petrović, Aleksandra Ristić-Fira
In most patients with lung cancer radiation treatment is used either as single agent or in combination with radiosensitizing drugs. However, the mechanisms underlying combined therapy and its impact on different modes of cell death have not yet been fully elucidated. We aimed to examine effects of single and combined treatments with γ-rays and erlotinib on radioresistant CRL-5876 human lung adenocarcinoma cells with particular emphasis on cell death. CRL-5876 cells were treated with γ-rays and/or erlotinib and changes in cell cycle, DNA repair dynamics, ultrastructure, nuclear morphology and protein expression were monitored at different time points...
April 2016: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/26990493/hypoxia-responsive-mir-124-and-mir-144-reduce-hypoxia-induced-autophagy-and-enhance-radiosensitivity-of%C3%A2-prostate%C3%A2-cancer-cells-via-suppressing-pim1
#13
Hao Gu, Mingzhu Liu, Changmao Ding, Xin Wang, Rui Wang, Xinyu Wu, Ruitai Fan
Cancer cells in hypoxia usually make adaptive changes in cellular metabolism, such as altered autophagy. This might be a cause of enhanced radioresistance in some types of cancer. In this study, we investigated hypoxia-responsive miRNAs in two prostate cancer cell lines (DU145 and PC3). This study firstly reported that hypoxia induces further downregulation of miR-124 and miR-144, which might be a result of impaired dicer expression. These two miRNAs can simultaneously target 3'UTR of PIM1. Functional study showed that miR-124 or miR-144 overexpression can inhibit hypoxia-induced autophagy and enhance radiosensitivity at least via downregulating PIM1...
June 2016: Cancer Medicine
https://www.readbyqxmd.com/read/26698406/resveratrol-a-potential-radiation-sensitizer-for-glioma-stem-cells-both-in%C3%A2-vitro-and-in%C3%A2-vivo
#14
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
https://www.readbyqxmd.com/read/26689155/long-term-autophagy-and-nrf2-signaling-in-the-hippocampi-of-developing-mice-after-carbon-ion-exposure
#15
Fei Ye, Ting Zhao, Xiongxiong Liu, Xiaodong Jin, Xinguo Liu, Tieshan Wang, Qiang Li
To explore charged particle radiation-induced long-term hippocampus damage, we investigated the expression of autophagy and antioxidant Nrf2 signaling-related proteins in the mouse hippocampus after carbon ion radiation. Heads of immature female Balb/c mice were irradiated with carbon ions of different LETs at various doses. Behavioral tests were performed on the mice after maturation. Acute and chronic expression of LC3-II, p62/SQSTM1, nuclear Nrf2, activated caspase-3 and the Bax/Bcl-2 ratio were measured in the hippocampi...
2015: Scientific Reports
https://www.readbyqxmd.com/read/26622795/microrna-32-induces-radioresistance-by-targeting-dab2ip-and-regulating-autophagy-in-prostate-cancer-cells
#16
Haiqiu Liao, Yang Xiao, Yingbin Hu, Yangming Xiao, Zhaofa Yin, Liang Liu
The aberrant expression of microRNAs (miRNAs/miRs) has been found in numerous cancer types. miR-32 is an oncomiR in prostate cancer (PCa), however, the mechanisms by which miR-32 functions as a regulator of radiotherapy response and resistance in PCa are largely unknown. In the present study, it was found that DAB2 interacting protein (DAB2IP), the miR-32-dependent tumor-suppressor gene, was downregulated and induced autophagy and inhibited radiotherapy-induced apoptosis in PCa cells. miR-32 expression was upregulated or overexpressed in PCa, and miR-32 inhibited DAB2IP expression through a direct binding site within the DAB2IP 3' untranslated region...
October 2015: Oncology Letters
https://www.readbyqxmd.com/read/26613064/autophagy-inhibition-to-increase-radiosensitization-in-breast-cancer
#17
Diana Hwang Liang, Randa El-Zein, Bhuvanesh Dave
Currently, many breast cancer patients with localized breast cancer undergo breast-conserving therapy, consisting of local excision followed by radiation therapy. Following radiation therapy, breast cancer cells are noted to undergo induction of autophagy, development of radioresistance, and enrichment of breast cancer stem cell subpopulations. It is hypothesized that inhibition of the cytoprotective autophagy that arises following radiation therapy increases radiosensitivity and confers longer relapse-free survival by eliminating tumor-initiating breast cancer stem cells...
2015: Journal of Nuclear Medicine & Radiation Therapy
https://www.readbyqxmd.com/read/26318663/ampk-independent-autophagy-promotes-radioresistance-of-human-tumor-cells-under-clinical-relevant-hypoxia-in-vitro
#18
Hassan Chaachouay, Birgit Fehrenbacher, Mahmoud Toulany, Martin Schaller, Gabriele Multhoff, H Peter Rodemann
BACKGROUND AND PURPOSE: Blocking of the autophagy-signaling has the potential to improve cancer therapy. In the present study, the role of autophagy for radioresistance of human tumor cells was tested under clinically relevant hypoxia (1% O2). MATERIALS AND METHODS: Non-small cell lung cancer cell lines A549 and H460, head and neck squamous cell carcinoma FaDu, colon carcinoma cell line HCT116 and mouse-embryo-fibroblasts were analyzed under normoxic (21% O2) and hypoxic (0...
September 2015: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/26203772/radio-resistant-mesenchymal-stem-cells-mechanisms-of-resistance-and-potential-implications-for-the-clinic
#19
REVIEW
Nils H Nicolay, Ramon Lopez Perez, Rainer Saffrich, Peter E Huber
Mesenchymal stem cells (MSCs) comprise a heterogeneous population of multipotent stromal cells and can be isolated from various tissues and organs. Due to their regenerative potential, they have been subject to intense research efforts, and they may provide an efficient means for treating radiation-induced tissue damage. MSCs are relatively resistant to ionizing radiation and retain their stem cell characteristics even after high radiation doses. The underlying mechanisms for the observed MSC radioresistance have been extensively studied and may involve efficient DNA damage recognition, double strand break repair and evasion of apoptosis...
August 14, 2015: Oncotarget
https://www.readbyqxmd.com/read/26134156/microrna-216a-enhances-the-radiosensitivity-of-pancreatic-cancer-cells-by-inhibiting-beclin-1-mediated-autophagy
#20
Xiangliang Zhang, Huijuan Shi, Shengqv Lin, Mingchen Ba, Shuzhong Cui
Radioresistance has become a challenge in the treatment of pancreatic cancer, which limits the efficacy and outcomes of radiotherapy in clinical treatment. Autophagy, recognized as an adaptive response to cell stress, has recently been involved in the radioresistance of cancer cells. MicroRNAs (miRNAs) are also involved in the radioresistance of pancreatic cancer cells. In the present study, we established a radioresistant pancreatic cancer cell line and found that miRNA-216a was significantly downregulated whereas the autophagy activity was increased as compared with the control...
September 2015: Oncology Reports
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