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HIF-1α AND tumor

Myung-Chul Kim, Sung-Hyun Hwang, Na-Yon Kim, Hong-Seok Lee, Sumin Ji, Yeseul Yang, Yongbaek Kim
BACKGROUND: Hypoxia is a hallmark of the solid tumor microenvironment and is associated with poor outcomes in cancer patients. The present study was performed to investigate mechanisms underlying the hypoxia-induced phenotypic changes using human malignant mesothelioma (HMM) cells. METHODS: Hypoxic conditions were achieved by incubating HMM cells in the air chamber. The effect of hypoxia on phenotype changes in HMM cells was investigated by performing in vitro clonogenicity, drug resistance, migration, and invasion assays...
August 15, 2018: BMC Cancer
Dongmei Ding, Manhui Zhu, Xiaojuan Liu, Li Jiang, Jiaowen Xu, Lili Chen, Juan Liang, Lele Li, Taohu Zhou, Ying Wang, Hao Shi, You Yuan, E Song
Choroidal neovascularization (CNV) is a type of wet age-related macular degeneration (AMD) which is a major cause of blindness in elder patients. Tumor necrosis factor receptor-associated factor 6 (TRAF6) promotes tumor angiogenesis via upregulating the expression of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF). Additionally, TRAF6 facilitates the inflammatory response in macrophages and microglia. Here, using mouse laser-induced CNV model and TRAF6 siRNA, the study shows that TRAF6 is a critical player in CNV...
August 6, 2018: Biochemical and Biophysical Research Communications
Yue Xing, Chunliu Mi, Zhe Wang, Zhi Hong Zhang, Ming Yue Li, Hong Xiang Zuo, Jing Ying Wang, Xuejun Jin, Juan Ma
Dictamnus dasycarpus is a traditional Chinese medicine that has been commonly used in the treatment of cancer. Fraxinellone is a natural product isolated from the D. dasycarpus plant, which has been shown to exhibit neuroprotective and anti-inflammatory activities. However, whether fraxinellone exerts anticancer effects and the mechanisms by which it may inhibit tumor growth remain unknown. Here, we found that fraxinellone, in a dose-dependented manner, inhibited the expression of programmed cell death ligand-1 (PD-L1), which plays a pivotal role in tumorigenesis...
August 10, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Lingtong Meng, Yali Cheng, Xiaoning Tong, Shaoju Gan, Yawen Ding, Yu Zhang, Chao Wang, Lei Xu, Yishen Zhu, Jinhui Wu, Yiqiao Hu, Ahu Yuan
Hypoxia, and hypoxia-inducible factor-1 (HIF-1), can induce tumor resistance to radiation therapy. To overcome hypoxia-induced radiation resistance, recent studies have described nano-systems to improve tumor oxygenation for immobilizing DNA damage and simultaneously initiate oxygen-dependent HIF-1α degradation. However, HIF-1α degradation is incomplete during tumor oxygenation treatment alone. Therefore, tumor oxygenation combined with residual HIF-1 functional inhibition is crucial to optimizing therapeutic outcomes of radiotherapy...
August 13, 2018: ACS Nano
Yanjing Li, Hong Sui, Cailing Jiang, Shumin Li, Yu Han, Peng Huang, Xiaoxue Du, Jingwen Du, Yuxian Bai
BACKGROUND/AIMS: Although photodynamic therapy (PDT) can relieve esophageal obstruction and prolong survival time of patients with esophageal cancer, it can induce nuclear factor-kappa B (NF-κB) activation in many cancers, which plays a negative role in PDT. Dihydroartemisinin (DHA), the most potent artemisinin derivative, can enhance the effect of PDT on esophageal cancer cells. However, the mechanism is still unclear. METHODS: We generated stable cell lines expressing the super-repressor form of the NF-κB inhibitor IκBα and cell lines with lentivirus vector-mediated silencing of the HIF-1α gene...
August 10, 2018: Cellular Physiology and Biochemistry
Hui Zhang, Qing Ye, Zhenfang Du, Min Huang, Ming Zhang, Huifeng Tan
MicroRNAs (miRNAs) have been implicated in a large number of biological processes such as tumor angiogenesis. MiR-148b-3p has been identified as a tumor suppressor in multiple cancer types and the function of miR-148b-3p in renal carcinoma remains unidentified. In this study, we found that the expression of miR-148b-3p was decreased in renal carcinoma based on GEO analysis and the gain-of-function experiments revealed that miR-148b-3p promoted renal carcinoma cell apoptosis and suppressed cell proliferation, migration in vitro and tumor growth in vivo...
August 9, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Yufei Yang, Yue Cao, Lihua Chen, Fei Liu, Zihao Qi, Xi Cheng, Ziliang Wang
Ovarian cancer is the most malignant gynecologic cancer among women worldwide. Cryptotanshinone (CT), isolated from Salvia miltiorrhiza Bunge, has been identified as a potential therapeutic agent in treating several malignant tumors, but the molecular mechanism of CT in ovarian cancer still remains illustrated. Here, we sought to elucidate the regulatory function of CT on cell glucose metabolism in ovarian cancer. The treatment of CT on ovarian cancer cells effectively inhibited glucose uptake and lactate production in ovarian cancer cells...
August 9, 2018: Cancer Medicine
Bei Tong, Vasiliki Pantazopoulou, Elinn Johansson, Alexander Pietras
Tumor hypoxia is associated with several features of aggressive glioma growth, including migration, invasion, and stemness. Most of the cellular adaptation to hypoxia is mediated by the hypoxia-inducible factors HIF-1α and HIF-2α, but regulation of these factors by both oxygen-dependent and -independent mechanisms in brain tumors is only partially understood. Here, we show that the p75 neurotrophin receptor (p75NTR ) is stabilized at hypoxia in murine glioma in vivo, as well as in primary human glioma cultures in vitro...
August 6, 2018: Experimental Cell Research
Ji Hye Hwang, Vinoth R Kumar, Seok Yong Kang, Hyo Won Jung, Yong-Ki Park
OBJECTIVE: To investigate the effects of the flower buds extract of Tussilago farfara Linné (Farfarae Flos; FF) on focal cerebral ischemia through regulation of inflammatory responses in activated microglia. METHODS: Brain ischemia was induced in Sprague-Dawley rats by a transient middle cerebral artery occlusion (tMCAO) for 90 min and reperfusion for 24 h. Twenty rats were randomly divided into 4 groups (n=5 per group): normal, tMCAO-induced ischemic control, tMCAO plus FF extract 300 mg/kg-treated, and tMCAO plus MK-801 1 mg/kg-treated as reference drug...
August 8, 2018: Chinese Journal of Integrative Medicine
Guo Chen Duan
Background: We investigated the combined effects of Kanglaite (KLT) and cisplatin on tumor associated macrophage (TAM) and expression of hypoxia inducible factor-1 alpha (HIF-1α) in Kunming mice with Lewis lung carcinoma. Methods: Kunming mice with Lewis lung carcinoma were randomly divided into four groups: the control (NS) group, KLT group, cisplatin (DDP) group and DDP+KLT group in Hebei People's Hospital, Hebei China from 2016 to 2017. Tumors were harvested 14 days after corresponding interventions...
June 2018: Iranian Journal of Public Health
Gang Wu, Gang Xu, De-Wei Chen, Wen-Xiang Gao, Jian-Qiong Xiong, Hai-Ying Shen, Yu-Qi Gao
Acute lung injury (ALI) is characterized by non-cardiogenic diffuse alveolar damage and often leads to a lethal consequence, particularly when hypoxia coexists. The treatment of ALI remains a challenge: pulmonary inflammation and hypoxia both contribute to its onset and progression and no effective prevention approach is available. Here, we aimed to investigate the underlying mechanism of hypoxia interaction with inflammation in ALI and to evaluate hypoxia-inducible factor 1 alpha (HIF-1α)-the crucial modulator in hypoxia-as a potential therapeutic target against ALI...
2018: Frontiers in Immunology
Hung-Jung Wang, Mamata Pochampalli, Ling-Yu Wang, June X Zou, Pei-Shan Li, Sheng-Chieh Hsu, Bi-Juan Wang, Shih-Han Huang, Ping Yang, Joy C Yang, Cheng-Ying Chu, Chia-Ling Hsieh, Shian-Ying Sung, Chien-Feng Li, Clifford G Tepper, David K Ann, Allen C Gao, Christopher P Evans, Yoshihiro Izumiya, Chi-Pin Chuu, Wen-Ching Wang, Hong-Wu Chen, Hsing-Jien Kung
During the evolution into castration or therapy resistance, prostate cancer cells reprogram the androgen responses to cope with the diminishing level of androgens, and undergo metabolic adaption to the nutritionally deprived and hypoxia conditions. AR (androgen receptor) and PKM2 (pyruvate kinase M2) have key roles in these processes. We report in this study, KDM8/JMJD5, a histone lysine demethylase/dioxygnase, exhibits a novel property as a dual coactivator of AR and PKM2 and as such, it is a potent inducer of castration and therapy resistance...
August 2, 2018: Oncogene
Toshiyuki Takemori, Teruya Kawamoto, Takeshi Ueha, Mitsunori Toda, Masayuki Morishita, Etsuko Kamata, Naomasa Fukase, Hitomi Hara, Shuichi Fujiwara, Takahiro Niikura, Ryosuke Kuroda, Toshihiro Akisue
Hypoxia plays a significant role in cancer progression, including metastatic bone tumors. We previously reported that transcutaneous carbon dioxide (CO2) application could decrease tumor progression through the improvement of intratumor hypoxia. Therefore, we hypothesized that decreased hypoxia using transcutaneous CO2 could suppress progressive bone destruction in cancer metastasis. In the present study, we examined the effects of transcutaneous CO2 application on metastatic bone destruction using an animal model...
July 30, 2018: Oncology Reports
Jian-Ching Wu, Han-En Tsai, Guei-Sheung Liu, Chieh-Shan Wu, Ming-Hong Tai
Hypoxia in tumors is known to trigger the pro-survival pathways such as autophagy. Systemic proopiomelanocortin (POMC) gene therapy suppresses melanoma through apoptosis induction and neovascularization blockage. In this study, we investigated the crosstalk between autophagic and apoptotic signaling in POMC-mediated melanoma suppression. By histological and immunoblot analysis, it was shown that POMC-treated melanoma tissues exhibited the prominent LC3 immunostaining, which was correlated with reduced CD31-positive tumor vascularization...
2018: Cell Death Discovery
Bin Yan, Zhengdong Jiang, Liang Cheng, Ke Chen, Cancan Zhou, Liankang Sun, Weikun Qian, Jie Li, Junyu Cao, Qinhong Xu, Qingyong Ma, Jianjun Lei
Pancreatic stellate cells (PSCs), a pivotal component of the tumor microenvironment, contribute to tumor growth and metastasis. PSC-derived factors are essential for triggering the generation and maintenance of cancer stem cells (CSCs). However, the mechanisms by which paracrine signals regulate CSC-like properties such as glycolytic metabolism have not been fully elucidated. Here, we report that two pancreatic cancer cell lines, Panc-1 and MiaPaCa-2, reacted differently when treated with hepatocyte growth factor (HGF) secreted from PSCs...
July 26, 2018: Experimental Cell Research
Ya-Yun Qian, You-Yang Shi, Song-Hua Lu, Ting Yang, Xue-Yu Zhao, Yan Yan, Wen-Yuan Li, Yan-Qing Liu
OBJECTIVE: To evaluate the effects of Celastrus Orbiculatus extracts (COE) on metastasis in hypoxia-induced hepatocellular carcinoma cells (HepG2) and to explore the underlying molecular mechanisms. METHODS: The effect of COE (160, 200 and 240 μg/mL) on cell viability, scratch-wound, invasion and migration were studied by 3-4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-H-tetrazolium bromide (MTT), scratch-wound and transwell assays, respectively. CoCl2 was used to establish a hypoxia model in vitro...
July 25, 2018: Chinese Journal of Integrative Medicine
Sonja Heller, Gabriele D Maurer, Christina Wanka, Ute Hofmann, Anna-Luisa Luger, Ines Bruns, Joachim P Steinbach, Johannes Rieger
In several tumor entities, transketolase-like protein 1 (TKTL1) has been suggested to promote the nonoxidative part of the pentose phosphate pathway (PPP) and thereby to contribute to a malignant phenotype. However, its role in glioma biology has only been sparsely documented. In the present in vitro study using LNT-229 glioma cells, we analyzed the impact of TKTL1 gene suppression on basic metabolic parameters and on survival following oxygen restriction and ionizing radiation. TKTL1 was induced by hypoxia and by hypoxia-inducible factor-1α (HIF-1α)...
July 25, 2018: International Journal of Molecular Sciences
Xu Li, Junjie Xing, Hantao Wang, Enda Yu
Growing evidence has uncovered that SLC34A2 plays an evident role in the progression in several types of tumors. However, the biological function and underlying molecular mechanisms of SLC34A2 remain largely unknown. Here, we indicated that SLC34A2 expression was markedly increased in SW480 and HT29 cell line cells compared with that in normal colorectal epithelial cell line cells. Array analysis displayed that the expression of EZH2 (enhancer of zeste 2) decreased considerably when SLC34A2 was knocked-down...
July 23, 2018: Bioscience Reports
Xiang Hu, Ya-Qi Li, Qing-Guo Li, Yan-Lei Ma, Jun-Jie Peng, San-Jun Cai
BACKGROUND: OGN could modify tissue inflammation and immune response via local and circulating innate immune cells, which was suggestive of a reciprocal relationship between OGN and T cell infiltration in cancer. Hence, we aim to measure the OGN expression patterns and immune cells response in colorectal cancer(CRC). METHODS: This study enrolled three independent sets of patients from TCGA and the Fudan University Shanghai Cancer Center(FUSCC). The effect of OGN on T cell infiltration and the mechanism were examined in vitro and in vivo...
July 20, 2018: EBioMedicine
Anja Weber, Helmut Klocker, Herbert Oberacher, Erich Gnaiger, Hannes Neuwirt, Natalie Sampson, Iris E Eder
The idea of using metabolic aberrations as targets for diagnosis or therapeutic intervention has recently gained increasing interest. In a previous study, our group discovered intriguing differences in the oxidative mitochondrial respiration capacity of benign and prostate cancer (PCa) cells. In particular, we found that PCa cells had a higher total respiratory activity than benign cells. Moreover, PCa cells showed a substantial shift towards succinate-supported mitochondrial respiration compared to benign cells, indicating a re-programming of respiratory control...
July 21, 2018: International Journal of Molecular Sciences
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