A novel mode of action of YC-1 in HIF inhibition: stimulation of FIH-dependent p300 dissociation from HIF-1α

Li, Shan Hua; Shin, Dong Hoon; Chun, Yang–Sook; Lee, Myung Kyu; Kim, Myung-Suk; Park, Jong-Wan

doi:10.1158/1535-7163.mct-08-0074

Cited by 146 publications

(84 citation statements)

References 42 publications

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“…23 Dong et al reported that hippocampal apoptosis was aggravated by YC-1, which was an inhibitor of HIF-1a and HIF-2a. 24,25 We found YC-1 effectively suppressed the protein level of HIF-1a and HIF-2a in AGE1.HN and PC12 cells exposed to hypoxia. When AGE1.HN and PC12 cells transfected with YC-1 or siHIF-1a or siHIF-2a and exposed to hypoxia, we found that YC-1 and siHIF-1a reversed the effect of hypoxia on .HN and PC12 cells were transfected with BCL-2 plasmid or controls and then exposed to hypoxia.…”

Section: Discussionmentioning

confidence: 74%

Hypoxia promotes apoptosis of neuronal cells through hypoxia-inducible factor-1α-microRNA-204-B-cell lymphoma-2 pathway

Wang

et al. 2015

Exp Biol Med (Maywood)

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Neuronal cells are highly sensitive to hypoxia and may be subjected to apoptosis when exposed to hypoxia. Several apoptosisrelated genes and miRNAs involve in hypoxia-induced apoptosis. This study aimed to examine the role of HIF1a-miR-204-BCL-2 pathway in hypoxia-induced apoptosis in neuronal cells. Annexin V/propidium iodide assay was performed to analyze cell apoptosis in AGE1.HN and PC12 cells under hypoxic or normoxic conditions. The expression of BCL-2 and miR-204 were determined by Western blot and qRT-PCR. The effects of miR-204 overexpression or knockdown on the expression of BCL-2 were evaluated by luciferase assay and Western blot under hypoxic or normoxic conditions. HIF-1a inhibitor YC-1 and siHIF-1a were employed to determine the effect of HIF-1a on the up-regulation of miR-204 and down-regulation of BCL-2 induced by hypoxia. Apoptosis assay showed the presence of apoptosis induced by hypoxia in neuronal cells. Moreover, we found that hypoxia significantly down-regulated the expression of BCL-2, and increased the mRNA level of miR-204 in neuronal cells than that in control. Bioinformatic analysis and luciferase reporter assay demonstrated that miR-204 directly targeted and regulated the expression of BCL-2. Specifically, the expression of BCL-2 was inhibited by miR-204 mimic and enhanced by miR-204 inhibitor. Furthermore, we detected that hypoxia induced cell apoptosis via HIF-1a/miR-204/BCL-2 in neuronal cells. This study demonstrated that HIF-1a-miR-204-BCL-2 pathway contributed to apoptosis of neuronal cells induced by hypoxia, which could potentially be exploited to prevent spinal cord ischemia-reperfusion injury.

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Section: Discussionmentioning

confidence: 74%

Hypoxia promotes apoptosis of neuronal cells through hypoxia-inducible factor-1α-microRNA-204-B-cell lymphoma-2 pathway

Wang

et al. 2015

Exp Biol Med (Maywood)

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“…YC-1 induces HIF-1a protein degradation (64), and it inhibits the translation of HIF-1a mRNA via suppression of the PI3K/AKT/mTOR pathway and Akt/NF-kB signaling (11). Furthermore, YC-1 regulates HIF-1a functional activity at the posttranslational level (65).…”

Section: Hif-1 Inhibition Tumor Microenvironment and Response To Ramentioning

confidence: 99%

Targeting Hypoxia, HIF-1, and Tumor Glucose Metabolism to Improve Radiotherapy Efficacy

Meijer

Kaanders

Span

et al. 2012

Clinical Cancer Research

384

344

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Radiotherapy, an important treatment modality in oncology, kills cells through induction of oxidative stress. However, malignant tumors vary in their response to irradiation as a consequence of resistance mechanisms taking place at the molecular level. It is important to understand these mechanisms of radioresistance, as counteracting them may improve the efficacy of radiotherapy. In this review, we describe how the hypoxia-inducible factor 1 (HIF-1) pathway has a profound effect on the response to radiotherapy. The main focus will be on HIF-1-controlled protection of the vasculature postirradiation and on HIF-1 regulation of glycolysis and the pentose phosphate pathway. This aberrant cellular metabolism increases the antioxidant capacity of tumors, thereby countering the oxidative stress caused by irradiation. From the results of translational studies and the first clinical phase I/II trials, it can be concluded that targeting HIF-1 and tumor glucose metabolism at several levels reduces the antioxidant capacity of tumors, affects the tumor microenvironment, and sensitizes various solid tumors to irradiation. Clin Cancer Res; 18(20); 5585-94. Ó2012 AACR.

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“…Hypoxia, a reduction in tissue oxygen tension due to inadequate oxygen supply, is a common phenomenon that occurs in a majority of solid tumours in humans (4). The presence of hypoxia is associated with aggressive tumour progression, resistance to chemotherapy and radiation, and poor prognosis (5,6).…”

Section: Introductionmentioning

confidence: 99%

Similarity in the functions of HIF‑1α and HIF‑2α proteins in cervical cancer cells

Jiang

Shi

et al. 2017

Oncol Lett

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Abstract. Hypoxia is a common feature of many solid tumours, including cervical cancer. Aggressive tumour progression is mostly associated with hypoxia. Furthermore, hypoxic conditions in tumours are also associated with resistance to chemotherapy and radiation, and with poor prognosis. Hypoxia inducible factor (HIF)-1, composed of a constitutively expressed β-subunit (HIF-β/ARNT) and one of the three known oxygen-regulated α-subunits, HIF-1α, HIF-2α, or HIF-3α, mediates the tumour cell response to hypoxia. The distinction between the roles of HIF-1α and HIF-2α in tumorigenesis is not clearly delineated. Therefore, the aim of the present study was to investigate the effect of HIF-2α on the characteristics of a cervical cancer cell line and to compare the functions of HIF-1α and HIF-2α. The present study demonstrated that the levels of HIF-1α and HIF-2α expression increased under hypoxic exposure compared with normoxia. The major difference was the temporal expression of HIF-1α and HIF-2α, with expression of the two proteins peaking at different time-points. In addition, HIF-1α and HIF-2α had similar effects on proliferation, cell cycle and apoptosis. Suppression of expression of HIF-1α or HIF-2α inhibited proliferation, induced G1-phase arrest and promoted apoptosis in the cervical cancer cell line CaSki. However, the effects of HIF-1α and HIF-2α on invasion and cell autophagy were different. The inhibitory effect of HIF-1α on cell invasion was stronger compared with HIF-2α, while the inhibitory effect of HIF-1α on cell autophagy was weaker compared with HIF-2α.Together, these results demonstrate that HIF-1α and HIF-2α have similar effects on the characteristics of a cervical cancer cell line. The major difference that the authors observed between the effects exerted by the two proteins on the cervical cancer cell line studied is the extent of their effect on invasion and autophagy.

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A novel mode of action of YC-1 in HIF inhibition: stimulation of FIH-dependent p300 dissociation from HIF-1α

Cited by 146 publications

References 42 publications

Hypoxia promotes apoptosis of neuronal cells through hypoxia-inducible factor-1α-microRNA-204-B-cell lymphoma-2 pathway

Hypoxia promotes apoptosis of neuronal cells through hypoxia-inducible factor-1α-microRNA-204-B-cell lymphoma-2 pathway

Targeting Hypoxia, HIF-1, and Tumor Glucose Metabolism to Improve Radiotherapy Efficacy

Similarity in the functions of HIF‑1α and HIF‑2α proteins in cervical cancer cells

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