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Celastrol Inhibits Migration and Invasion of Triple-Negative Breast Cancer Cells by Suppressing Interleukin-6 via Downregulating Nuclear Factor-κB (NF-κB)

BACKGROUND: Celastrol is extracted from the root of the Chinese traditional herb Tripterygium wilfordii, which has anti-cancer effects in multiple cancers. However, the effect of celastrol on the metastasis of triple-negative breast cancer and its mechanism remain largely unknown. MATERIAL/METHODS:...

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Autores principales: Yan, Fei, Wu, Zihong, Li, Zihui, Liu, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scientific Literature, Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510174/
https://www.ncbi.nlm.nih.gov/pubmed/32920591
http://dx.doi.org/10.12659/MSM.922814
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author Yan, Fei
Wu, Zihong
Li, Zihui
Liu, Li
author_facet Yan, Fei
Wu, Zihong
Li, Zihui
Liu, Li
author_sort Yan, Fei
collection PubMed
description BACKGROUND: Celastrol is extracted from the root of the Chinese traditional herb Tripterygium wilfordii, which has anti-cancer effects in multiple cancers. However, the effect of celastrol on the metastasis of triple-negative breast cancer and its mechanism remain largely unknown. MATERIAL/METHODS: MDA-MB-468 and MDA-MB-231 cells were treated with various doses of celastrol for 24 h. Cell viability was measured via MTT analysis. Cell migration and invasion were detected via transwell analysis. The expression of interleukin-6 (IL-6) was measured after transfection of short-hairpin RNA against IL-6 or celastrol treatment via quantitative real-time polymerase chain reaction, Western blot, or enzyme-linked immunosorbent analysis (ELISA). The protein levels in the nuclear factor-κB (NF-κB) pathway were measured by Western blot. The interaction between celastrol and NF-κB-mediated IL-6 was investigated by luciferase reporter assay. RESULTS: High concentrations of celastrol inhibited viability of MDA-MB-468 and MDA-MB-231 cells, but low doses of celastrol showed little effect on cell viability. Low doses of celastrol suppressed cell migration and invasion, and knockdown of IL-6 also repressed cell migration and invasion. Moreover, treatment with celastrol decreased IL-6 expression at mRNA and protein levels. IL-6 overexpression mitigated celastrol-mediated suppression of cell migration and invasion. Additionally, celastrol blocked the NF-κB pathway to inhibit IL-6 levels. CONCLUSIONS: Celastrol repressed migration and invasion through decreasing IL-6 levels by inactivation of NF-κB signaling in triple-negative breast cancer cells, providing a novel basis for use of celastrol in treating triple-negative breast cancer.
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spelling pubmed-75101742020-10-02 Celastrol Inhibits Migration and Invasion of Triple-Negative Breast Cancer Cells by Suppressing Interleukin-6 via Downregulating Nuclear Factor-κB (NF-κB) Yan, Fei Wu, Zihong Li, Zihui Liu, Li Med Sci Monit Clinical Research BACKGROUND: Celastrol is extracted from the root of the Chinese traditional herb Tripterygium wilfordii, which has anti-cancer effects in multiple cancers. However, the effect of celastrol on the metastasis of triple-negative breast cancer and its mechanism remain largely unknown. MATERIAL/METHODS: MDA-MB-468 and MDA-MB-231 cells were treated with various doses of celastrol for 24 h. Cell viability was measured via MTT analysis. Cell migration and invasion were detected via transwell analysis. The expression of interleukin-6 (IL-6) was measured after transfection of short-hairpin RNA against IL-6 or celastrol treatment via quantitative real-time polymerase chain reaction, Western blot, or enzyme-linked immunosorbent analysis (ELISA). The protein levels in the nuclear factor-κB (NF-κB) pathway were measured by Western blot. The interaction between celastrol and NF-κB-mediated IL-6 was investigated by luciferase reporter assay. RESULTS: High concentrations of celastrol inhibited viability of MDA-MB-468 and MDA-MB-231 cells, but low doses of celastrol showed little effect on cell viability. Low doses of celastrol suppressed cell migration and invasion, and knockdown of IL-6 also repressed cell migration and invasion. Moreover, treatment with celastrol decreased IL-6 expression at mRNA and protein levels. IL-6 overexpression mitigated celastrol-mediated suppression of cell migration and invasion. Additionally, celastrol blocked the NF-κB pathway to inhibit IL-6 levels. CONCLUSIONS: Celastrol repressed migration and invasion through decreasing IL-6 levels by inactivation of NF-κB signaling in triple-negative breast cancer cells, providing a novel basis for use of celastrol in treating triple-negative breast cancer. International Scientific Literature, Inc. 2020-09-13 /pmc/articles/PMC7510174/ /pubmed/32920591 http://dx.doi.org/10.12659/MSM.922814 Text en © Med Sci Monit, 2020 This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) )
spellingShingle Clinical Research
Yan, Fei
Wu, Zihong
Li, Zihui
Liu, Li
Celastrol Inhibits Migration and Invasion of Triple-Negative Breast Cancer Cells by Suppressing Interleukin-6 via Downregulating Nuclear Factor-κB (NF-κB)
title Celastrol Inhibits Migration and Invasion of Triple-Negative Breast Cancer Cells by Suppressing Interleukin-6 via Downregulating Nuclear Factor-κB (NF-κB)
title_full Celastrol Inhibits Migration and Invasion of Triple-Negative Breast Cancer Cells by Suppressing Interleukin-6 via Downregulating Nuclear Factor-κB (NF-κB)
title_fullStr Celastrol Inhibits Migration and Invasion of Triple-Negative Breast Cancer Cells by Suppressing Interleukin-6 via Downregulating Nuclear Factor-κB (NF-κB)
title_full_unstemmed Celastrol Inhibits Migration and Invasion of Triple-Negative Breast Cancer Cells by Suppressing Interleukin-6 via Downregulating Nuclear Factor-κB (NF-κB)
title_short Celastrol Inhibits Migration and Invasion of Triple-Negative Breast Cancer Cells by Suppressing Interleukin-6 via Downregulating Nuclear Factor-κB (NF-κB)
title_sort celastrol inhibits migration and invasion of triple-negative breast cancer cells by suppressing interleukin-6 via downregulating nuclear factor-κb (nf-κb)
topic Clinical Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510174/
https://www.ncbi.nlm.nih.gov/pubmed/32920591
http://dx.doi.org/10.12659/MSM.922814
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