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autophagy and IR and cancer

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)2Ir(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
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
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
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
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
Byeong Mo Kim, Yunkyung Hong, Seunghoon Lee, Pengda Liu, Ji Hong Lim, Yong Heon Lee, Tae Ho Lee, Kyu Tae Chang, Yonggeun Hong
Ionizing radiation (IR), such as X-rays and gamma (γ)-rays, mediates various forms of cancer cell death such as apoptosis, necrosis, autophagy, mitotic catastrophe, and senescence. Among them, apoptosis and mitotic catastrophe are the main mechanisms of IR action. DNA damage and genomic instability contribute to IR-induced cancer cell death. Although IR therapy may be curative in a number of cancer types, the resistance of cancer cells to radiation remains a major therapeutic problem. In this review, we describe the morphological and molecular aspects of various IR-induced types of cell death...
2015: International Journal of Molecular Sciences
Zongyan Chen, Benli Wang, Feifei Yu, Qiao Chen, Yuxi Tian, Shumei Ma, Xiaodong Liu
Mitochondria as the critical powerhouse of eukaryotic cells play important roles in regulating cell survival or cell death. Under numerous stimuli, impaired mitochondria will generate massive reactive oxygen species (ROS) which participate in the regulation of vital signals and could even determine the fate of cancer cells. While the roles of mitochondria in radiation-induced autophagic cell death still need to be elucidated. Human cervical cancer cell line, Hela, was used, and the SOD2 silencing model (SOD2-Ri) was established by gene engineering...
March 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Nan Liang, Rui Zhong, Xue Hou, Gang Zhao, Shumei Ma, Guanghui Cheng, Xiaodong Liu
OBJECTIVES: The role of Ataxia-telangiectasia mutated (ATM) in response to DNA damage has previously been studied, but its underlying mechanisms specific to ionizing radiation (IR) have remained to be elucidated. In this study, function of ATM on radiation-induced cell death in lung cancer H1299 cells was analysed. MATERIALS AND METHODS: Human lung cancer cells, H1299, were used, and cell models with ATM(-/-) and MAPK14(-/-) were established by genetic engineering...
October 2015: Cell Proliferation
Hui-Wen Chiu, Shu-Wen Lin, Li-Ching Lin, Yung-Ho Hsu, Yuh-Feng Lin, Sheng-Yow Ho, Yuan-Hua Wu, Ying-Jan Wang
Ninety percent of human pancreatic cancer is characterized by activating K-RAS mutations. TRAF6 is an oncogene that plays a vital role in K-RAS-mediated oncogenesis. We investigated the synergistic effect of combining ionizing radiation (IR) and proteasome inhibitor (MG132). Furthermore, following combined treatment with IR and MG132, we analyzed the expression of TRAF6 and the mechanism of human pancreatic cancer cell death in vitro and in an orthotopic pancreatic cancer mouse model. The combined treatment groups displayed synergistic cell killing effects and induced endoplasmic reticulum stress in human pancreatic cancer cells...
September 1, 2015: Cancer Letters
Rui Zhong, Huiying Xu, Ge Chen, Gang Zhao, Yan Gao, Xiaodong Liu, Shumei Ma, Lihua Dong
Hypoxia-inducible factor-1α (HIF-1α) is a major effector in cell survival response to hypoxia, while the roles of HIF-1α in radiation-induced autophagy are still unclear in breast cancer cells. Human breast cancer carcinoma MCF-7 cells were stably transfected with pSUPER-shRNA against human HIF-1α or a scrambled sequence with no homology to mammalian genes, named as pSUPER-HIF-1α and pSUPER-SC, respectively. Cell Counting Kit-8 (CCK-8) assay and colony formation assay were used to detect cell viability, Western blot was used to detect protein expression, monodansylcadaverine (MDC) staining was used to analyze autophagy, and Hoechts/PI staining was used to assess apoptosis...
September 2015: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Marco B E Schaaf, Barry Jutten, Tom G Keulers, Kim G M Savelkouls, Hanneke J M Peeters, Twan van den Beucken, Frederik-Jan van Schooten, Roger W Godschalk, Marc Vooijs, Kasper M A Rouschop
BACKGROUND: (Pre)clinical studies indicate that autophagy inhibition increases response to anti-cancer therapies. Although promising, due to contradicting reports, it remains unclear if radiation therapy changes autophagy activity and if autophagy inhibition changes the cellular intrinsic radiosensitivity. Discrepancies may result from different assays and models through off-target effects and influencing other signaling routes. In this study, we directly compared the effects of genetic and pharmacological inhibition of autophagy after irradiation in human cancer cell lines...
March 2015: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
Lan Yu, Zeng-Fu Shang, Feng-Ming Hsu, Zhang Zhang, Vasu Tumati, Yu-Fen Lin, Benjamin P C Chen, Debabrata Saha
The current standard of care for lung cancer consists of concurrent chemotherapy and radiation. Several studies have shown that the DNA-PKcs inhibitor NU7441 is a highly potent radiosensitizer, however, the mechanism of NU7441's anti-proliferation effect has not been fully elucidated. In this study, the combined effect of NU7441 and ionizing radiation (IR) in a panel of non-small cell lung cancer cell lines (A549, H460 and H1299) has been investigated. We found that NU7441 significantly enhances the effect of IR in all cell lines...
February 28, 2015: Oncotarget
Yuxia Cui, Stela S Palii, Cynthia L Innes, Richard S Paules
DNA damage response (DDR) to double strand breaks is coordinated by 3 phosphatidylinositol 3-kinase-related kinase (PIKK) family members: the ataxia-telangiectasia mutated kinase (ATM), the ATM and Rad3-related (ATR) kinase and the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs). ATM and ATR are central players in activating cell cycle checkpoints and function as an active barrier against genome instability and tumorigenesis in replicating cells. Loss of ATM function is frequently reported in various types of tumors, thus placing more reliance on ATR for checkpoint arrest and cell survival following DNA damage...
2014: Cell Cycle
Mao-Bin Meng, Huan-Huan Wang, Wen-Hao Guo, Zhi-Qiang Wu, Xian-Liang Zeng, Nicholas G Zaorsky, Hua-Shan Shi, Dong Qian, Zhi-Min Niu, Bo Jiang, Lu-Jun Zhao, Zhi-Yong Yuan, Ping Wang
Aerobic glycolysis, a metabolic hallmark of cancer, is associated with radioresistance in non-small cell lung cancer (NSCLC). Pyruvate kinase M2 isoform (PKM2), a key regulator of glycolysis, is expressed exclusively in cancers. However, the impact of PKM2 silencing on the radiosensitivity of NSCLC has not been explored. Here, we show a plasmid of shRNA-PKM2 for expressing a short hairpin RNA targeting PKM2 (pshRNA-PKM2) and demonstrate that treatment with pshRNA-PKM2 effectively inhibits PKM2 expression in NSCLC cell lines and xenografts...
January 28, 2015: Cancer Letters
Gizachew Yismaw Wubetu, Tohru Utsunomiya, Daichi Ishikawa, Tetsuya Ikemoto, Shinichiro Yamada, Yuji Morine, Shuichi Iwahashi, Yu Saito, Yusuke Arakawa, Satoru Imura, Hideki Arimochi, Mitsuo Shimada
BACKGROUND: Branched chain amino acid (BCAA) dietary supplementation inhibits activation of the insulin-like growth factor (IGF)/IGF-I receptor (IGF-IR) axis in diabetic animal models. However, the in vitro effect of BCAA on human cancer cell lines under hyper-insulinemic conditions remains unclear. MATERIALS AND METHODS: Colon (HCT-116) and hepatic (HepG2) tumor cells were treated with varying concentrations of BCAA with or without fluorouracil (5-FU). The effect of BCAA on insulin-initiated proliferation was determined...
September 2014: Anticancer Research
Ning Mo, Yong-Kui Lu, Wei-Min Xie, Yan Liu, Wen-Xian Zhou, Hong-Xue Wang, Li Nong, Yu-Xian Jia, Ai-Hua Tan, Ying Chen, Shan-Shan Li, Bao-Hua Luo
Radiotherapy has long been considered as the mainstay of treatment for nasopharyngeal carcinoma (NPC). However, locoregional recurrence or distant metastasis may occur in some patients due to the radiation resistance of cancer cells. Autophagy plays a vital role in protecting cells against radiation. However, the mechanism of autophagy in radiation therapy remains obscure. In the present study, we demonstrated that suppression of autophagy related 5 (Atg5) aggravated ionizing radiation (IR)-induced DNA damage and apoptosis in human NPC cells without accelerating the cell cycle, whereas regulation of the cell cycle has been widely regarded as the most important determinant of IR sensitivity...
November 2014: Oncology Reports
Suman Kumar Tripathy, Umasankar De, Niranjan Dehury, Satyanarayan Pal, Hyung Sik Kim, Srikanta Patra
Phpy bridged homodinuclear Ru-Ru () and heterodinuclear Ir-Ru complexes () have been developed. Complex induces autophagy towards the cisplatin resistant human breast cancer (MCF7) cell line, whereas is inactive.
October 21, 2014: Dalton Transactions: An International Journal of Inorganic Chemistry
Lan-Hui Li, Ping Wu, Jen-Yi Lee, Pei-Rong Li, Wan-Yu Hsieh, Chao-Chi Ho, Chen-Lung Ho, Wan-Jiun Chen, Chien-Chun Wang, Muh-Yong Yen, Shun-Min Yang, Huei-Wen Chen
Despite good initial responses, drug resistance and disease recurrence remain major issues for lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutations taking EGFR-tyrosine kinase inhibitors (TKI). To discover new strategies to overcome this issue, we investigated 40 essential oils from plants indigenous to Taiwan as alternative treatments for a wide range of illnesses. Here, we found that hinokitiol, a natural monoterpenoid from the heartwood of Calocedrus formosana, exhibited potent anticancer effects...
2014: PloS One
Min Liu, Shumei Ma, Mingbo Liu, Yufei Hou, Bing Liang, Xu Su, Xiaodong Liu
Cisplatin is a commonly used drug for chemotherapy, however, whether it may be used synergistically with radiotherapy remains unclear. The present study investigated the underlying mechanisms of synergistic killing by radiosensitization and cisplatin, with a focus on the growth inhibition, apoptosis and autophagy of non-small cell human lung cancer cells in vitro and in a tumor xenograft in vivo. A549 cells were used for the in vitro experiments and divided into the following four treatment groups: Sham-irradiated; conventional radiotherapy (CRT) of five doses of 2 Gy every day; hyperfractionated radiotherapy of five doses of 2 Gy (1 Gy twice a day at 4 h intervals) every day; and CRT plus cisplatin...
June 2014: Oncology Letters
Emel Saglar, Sibel Unlu, Ibrahim Babalioglu, Saban Cakir Gokce, Hatice Mergen
Acute radiation leads to several toxic clinical states and triggers some molecular pathways. To shed light on molecular mechanisms triggered by ionizing radiation (IR), we examined the expression profiles of endoplasmic reticulum (ER) stress and autophagy-related genes in individuals who were exposed to IR. Blood samples were collected from 50 cancer patients before radiotherapy and on the 5th, 15th, and 25th days of the treatment. Peripheral blood samples from 10 healthy volunteers were also obtained for ex vivo irradiation, divided into five and irradiated at a rate of 373 kGy/h to 0, 0...
September 2014: Journal of Biochemical and Molecular Toxicology
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