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Thymoquinone Selectively Kills Hypoxic Renal Cancer Cells by Suppressing HIF-1α-Mediated Glycolysis
Several reports have shown that thymoquinone (TQ) effectively attenuates angiogenesis in cancer cells, resulting in suppression of tumor growth. However, it is not yet clear whether TQ reduces hypoxia-inducible factor-1α (HIF-1α) expression in hypoxic cancer cells. Here, we found that TQ was a novel...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429094/ https://www.ncbi.nlm.nih.gov/pubmed/30832444 http://dx.doi.org/10.3390/ijms20051092 |
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author | Lee, Yoon-Mi Kim, Geon-Hee Park, Eun-Ji Oh, Taek-In Lee, Sujin Kan, Sang-Yeon Kang, Hyeji Kim, Byeong Mo Kim, Ji Hyung Lim, Ji-Hong |
author_facet | Lee, Yoon-Mi Kim, Geon-Hee Park, Eun-Ji Oh, Taek-In Lee, Sujin Kan, Sang-Yeon Kang, Hyeji Kim, Byeong Mo Kim, Ji Hyung Lim, Ji-Hong |
author_sort | Lee, Yoon-Mi |
collection | PubMed |
description | Several reports have shown that thymoquinone (TQ) effectively attenuates angiogenesis in cancer cells, resulting in suppression of tumor growth. However, it is not yet clear whether TQ reduces hypoxia-inducible factor-1α (HIF-1α) expression in hypoxic cancer cells. Here, we found that TQ was a novel HIF-1α inhibitor through hypoxia response element (HRE)-luciferase assay-based large screening by using 502 natural compounds containing chemical library. TQ reduced HIF-1α protein levels in renal cancer cells; however, it did not affect the HIF-1α protein levels in the presence of proteasome inhibitor, MG132, indicating that the reduction effects of TQ on HIF-1α protein are mediated via the ubiquitination-proteasome dependent pathway. TQ boosted HIF-1α protein degradation, and the mechanism was revealed by inhibiting interaction between HSP90 and HIF-1α. TQ suppressed downstream genes of HIF-1α, indicating negative impact of TQ on HIF-1α transcriptional activities. In addition, TQ altered glucose, lactate, and ATP levels, leading to anaerobic metabolic disturbance. TQ induced apoptosis in hypoxic cancer cells as determined by crystal violet staining and flow cytometry for annexin V-stained cells. Taken together, we suggested that TQ is a potential anticancer agent targeting HIF-1α. |
format | Online Article Text |
id | pubmed-6429094 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-64290942019-04-10 Thymoquinone Selectively Kills Hypoxic Renal Cancer Cells by Suppressing HIF-1α-Mediated Glycolysis Lee, Yoon-Mi Kim, Geon-Hee Park, Eun-Ji Oh, Taek-In Lee, Sujin Kan, Sang-Yeon Kang, Hyeji Kim, Byeong Mo Kim, Ji Hyung Lim, Ji-Hong Int J Mol Sci Article Several reports have shown that thymoquinone (TQ) effectively attenuates angiogenesis in cancer cells, resulting in suppression of tumor growth. However, it is not yet clear whether TQ reduces hypoxia-inducible factor-1α (HIF-1α) expression in hypoxic cancer cells. Here, we found that TQ was a novel HIF-1α inhibitor through hypoxia response element (HRE)-luciferase assay-based large screening by using 502 natural compounds containing chemical library. TQ reduced HIF-1α protein levels in renal cancer cells; however, it did not affect the HIF-1α protein levels in the presence of proteasome inhibitor, MG132, indicating that the reduction effects of TQ on HIF-1α protein are mediated via the ubiquitination-proteasome dependent pathway. TQ boosted HIF-1α protein degradation, and the mechanism was revealed by inhibiting interaction between HSP90 and HIF-1α. TQ suppressed downstream genes of HIF-1α, indicating negative impact of TQ on HIF-1α transcriptional activities. In addition, TQ altered glucose, lactate, and ATP levels, leading to anaerobic metabolic disturbance. TQ induced apoptosis in hypoxic cancer cells as determined by crystal violet staining and flow cytometry for annexin V-stained cells. Taken together, we suggested that TQ is a potential anticancer agent targeting HIF-1α. MDPI 2019-03-03 /pmc/articles/PMC6429094/ /pubmed/30832444 http://dx.doi.org/10.3390/ijms20051092 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Lee, Yoon-Mi Kim, Geon-Hee Park, Eun-Ji Oh, Taek-In Lee, Sujin Kan, Sang-Yeon Kang, Hyeji Kim, Byeong Mo Kim, Ji Hyung Lim, Ji-Hong Thymoquinone Selectively Kills Hypoxic Renal Cancer Cells by Suppressing HIF-1α-Mediated Glycolysis |
title | Thymoquinone Selectively Kills Hypoxic Renal Cancer Cells by Suppressing HIF-1α-Mediated Glycolysis |
title_full | Thymoquinone Selectively Kills Hypoxic Renal Cancer Cells by Suppressing HIF-1α-Mediated Glycolysis |
title_fullStr | Thymoquinone Selectively Kills Hypoxic Renal Cancer Cells by Suppressing HIF-1α-Mediated Glycolysis |
title_full_unstemmed | Thymoquinone Selectively Kills Hypoxic Renal Cancer Cells by Suppressing HIF-1α-Mediated Glycolysis |
title_short | Thymoquinone Selectively Kills Hypoxic Renal Cancer Cells by Suppressing HIF-1α-Mediated Glycolysis |
title_sort | thymoquinone selectively kills hypoxic renal cancer cells by suppressing hif-1α-mediated glycolysis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429094/ https://www.ncbi.nlm.nih.gov/pubmed/30832444 http://dx.doi.org/10.3390/ijms20051092 |
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