Docosahexaenoic Acid Inhibits Superoxide Dismutase 1 Gene Transcription in Human Cancer Cells: The Involvement of Peroxisome Proliferator-Activated Receptor α and Hypoxia-Inducible Factor-2α Signaling

2009 ◽  
Vol 76 (3) ◽  
pp. 588-595 ◽  
Author(s):  
Erin R. Tuller ◽  
Charles T. Beavers ◽  
Jessica R. Lou ◽  
Michael A. Ihnat ◽  
Doris M. Benbrook ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Docosahexaenoic Acid ◽  
Cancer Cells ◽  
Gene Transcription ◽  
Human Cancer ◽  
Hypoxia Inducible Factor ◽  
Peroxisome Proliferator ◽  
Superoxide Dismutase 1 ◽  
Peroxisome Proliferator Activated Receptor ◽  
Human Cancer Cells

scholarly journals A novel peroxisome proliferator-activated receptor delta antagonist, SR13904, has anti-proliferative activity in human cancer cells

2009 ◽  
Vol 8 (13) ◽  
pp. 1252-1261 ◽  
Author(s):  
Nurulain T. Zaveri ◽  
Barbara G. Sato ◽  
Faming Jiang ◽  
Joy Calaoagan ◽  
Keith Laderoute ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Proliferative Activity ◽  
Human Cancer ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Human Cancer Cells

A novel peroxisome proliferator-activated receptor α/γ agonist, BPR1H0101, inhibits topoisomerase II catalytic activity in human cancer cells

2008 ◽  
Vol 19 (2) ◽  
pp. 151-158 ◽  
Author(s):  
Yu-Hsun Kao ◽  
Hsing-Pang Hsieh ◽  
Santhosh Kumar Chitlimalla ◽  
Wen-Yu Pan ◽  
Ching-Chuan Kuo ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Cancer Cells ◽  
Topoisomerase Ii ◽  
Human Cancer ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Human Cancer Cells

scholarly journals Activation of Peroxisome Proliferator-activated Receptor α (PPARα) Suppresses Hypoxia-inducible Factor-1α (HIF-1α) Signaling in Cancer Cells

2012 ◽  
Vol 287 (42) ◽  
pp. 35161-35169 ◽  
Author(s):  
Jundong Zhou ◽  
Shuyu Zhang ◽  
Jing Xue ◽  
Jori Avery ◽  
Jinchang Wu ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Hypoxia Inducible Factor ◽  
Proteasome Inhibitors ◽  
Tube Formation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Hypoxia Inducible Factor 1Α ◽  
Anticancer Properties ◽  
Pparγ Agonist ◽  
Expression And Activity

Activation of peroxisome proliferator-activated receptor α (PPARα) has been demonstrated to inhibit tumor growth and angiogenesis, yet the mechanisms behind these actions remain to be characterized. In this study, we examined the effects of PPARα activation on the hypoxia-inducible factor-1α (HIF-1α) signaling pathway in human breast (MCF-7) and ovarian (A2780) cancer cells under hypoxia. Incubation of cancer cells under 1% oxygen for 16 h significantly induced HIF-1α expression and activity as assayed by Western blotting and reporter gene analysis. Treatment of the cells with PPARα agonists, but not a PPARγ agonist, prior to hypoxia diminished hypoxia-induced HIF-1α expression and activity, and addition of a PPARα antagonist attenuated the suppression of HIF-1α signaling. Activation of PPARα attenuated hypoxia-induced HA-tagged HIF-1α protein expression without affecting the HA-tagged HIF-1α mutant protein level, indicating that PPARα activation promotes HIF-1α degradation in these cells. This was further confirmed using proteasome inhibitors, which reversed PPARα-mediated suppression of HIF-1α expression under hypoxia. Using the co-immunoprecipitation technique, we found that activation of PPARα enhances the binding of HIF-1α to von Hippel-Lindau tumor suppressor (pVHL), a protein known to mediate HIF-1α degradation through the ubiquitin-proteasome pathway. Following PPARα-mediated suppression of HIF-1α signaling, VEGF secretion from the cancer cells was significantly reduced, and tube formation by endothelial cells was dramatically impaired. Taken together, these findings demonstrate for the first time that activation of PPARα suppresses hypoxia-induced HIF-1α signaling in cancer cells, providing novel insight into the anticancer properties of PPARα agonists.

scholarly journals Sphingosine Kinase 1: A New Modulator of Hypoxia Inducible Factor 1α during Hypoxia in Human Cancer Cells

2008 ◽  
Vol 68 (20) ◽  
pp. 8635-8642 ◽  
Author(s):  
Isabelle Ader ◽  
Leyre Brizuela ◽  
Pierre Bouquerel ◽  
Bernard Malavaud ◽  
Olivier Cuvillier
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Hypoxia Inducible Factor ◽  
Sphingosine Kinase ◽  
Sphingosine Kinase 1 ◽  
Hypoxia Inducible Factor 1Α ◽  
Human Cancer Cells

scholarly journals Docosahexaenoic acid induces autophagy through p53/AMPK/mTOR signaling and promotes apoptosis in human cancer cells harboring wild-type p53

Autophagy ◽  
2011 ◽  
Vol 7 (11) ◽  
pp. 1348-1358 ◽  
Author(s):  
Kaipeng Jing ◽  
Kyoung-Sub Song ◽  
Soyeon Shin ◽  
Nayeong Kim ◽  
Soyeon Jeong ◽  
...  
Keyword(s):  
Docosahexaenoic Acid ◽  
Cancer Cells ◽  
Human Cancer ◽  
Mtor Signaling ◽  
Wild Type ◽  
Human Cancer Cells ◽  
Wild Type P53

scholarly journals Transcriptome sequencing revealed differences in the response of renal cancer cells to hypoxia and CoCl2 treatment

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 1518 ◽  
Author(s):  
Nadezhda Zhigalova ◽  
Artem Artemov ◽  
Alexander M. Mazur ◽  
Egor B. Prokhortchouk
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Hypoxia Inducible Factor ◽  
Low Oxygen ◽  
Human Cancer Cells ◽  
Hypoxic Conditions ◽  
Pathway Activation ◽  
Oxygen Conditions ◽  
Order Of Magnitude ◽  
Transcriptional Changes

Human cancer cells are subjected to hypoxic conditions in many tumours. Hypoxia causes alterations in the glycolytic pathway activation through stabilization of hypoxia-inducible factor 1. Currently, two approaches are commonly used to model hypoxia: an alternative to generating low-oxygen conditions in an incubator, cells can be treated with CoCl2. We performed RNA-seq experiments to study transcriptomes of human Caki-1 cells under real hypoxia and after CoCl2 treatment. Despite causing transcriptional changes of a much higher order of magnitude for the genes in the hypoxia regulation pathway, CoCl2 treatment fails to induce alterations in the glycolysis / gluconeogenesis pathway. Moreover, CoCl2 caused aberrant activation of other oxidoreductases in glycine, serine and threonine metabolism pathways.

Abstract 2867: Docosahexaenoic acid induces autophagy through p53/AMPK/mTOR signaling in human cancer cells

2011 ◽  
Author(s):  
Kiapeng Jing ◽  
Kyoung-Sub Song ◽  
Soyeon Shin ◽  
Nayeong Kim Kim ◽  
Soyeon Jeong ◽  
...  
Keyword(s):  
Docosahexaenoic Acid ◽  
Cancer Cells ◽  
Human Cancer ◽  
Mtor Signaling ◽  
Human Cancer Cells

Anoxic induction of ATF-4 through HIF-1–independent pathways of protein stabilization in human cancer cells

Blood ◽  
2004 ◽  
Vol 103 (5) ◽  
pp. 1876-1882 ◽  
Author(s):  
Kurosh Ameri ◽  
Claire E. Lewis ◽  
Martin Raida ◽  
Heidi Sowter ◽  
Tsonwin Hai ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cancer Cells ◽  
Human Cancer ◽  
Hypoxia Inducible Factor ◽  
Tumor Development ◽  
Oxygen Depletion ◽  
Protein Stabilization ◽  
Von Hippel Lindau ◽  
Human Cancer Cells ◽  
Key Factor

Abstract Hypoxia is a key factor in tumor development, contributing to angiogenesis and radiotherapy resistance. Hypoxia-inducible factor-1 (HIF-1) is a major transcription factor regulating the response of cancer cells to hypoxia. However, tumors also contain areas of more severe oxygen depletion, or anoxia. Mechanisms for survival under anoxia are HIF-1α independent in Caenorhabditis elegans and, thus, differ from the hypoxic response. Here we report a differential response of cancer cells to hypoxia and anoxia by demonstrating the induction of activating transcription factor-4 (ATF-4) and growth arrest DNA damage 153 (GADD153) protein specifically in anoxia and the lack of induction in hypoxia. By applying RNAi, ATF-4 induction in anoxia was shown to be independent of HIF-1α, and desferrioxamine mesylate (DFO) and cobalt chloride induced HIF-1α but not ATF-4 or GADD153. Furthermore, the inductive response of ATF-4 and GADD153 was not related to alterations in or arrest of mitochondrial respiration and was independent of von Hippel-Lindau (VHL) disease mutations. In reoxygenated anoxic cells, ATF-4 had a half-life of less than 5 minutes; adding the proteasome inhibitor to normoxic cells up-regulated ATF-4 protein. Extracts from primary human tumors demonstrated more ATF-4 expression in tumors near necrotic areas. Thus, this study demonstrates a novel HIF-1α–independent anoxic mechanism that regulates ATF-4 induction at the protein stability level in tumor cells.

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