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Dimethyl Fumarate Induces Apoptosis via Inhibition of NF-κB and Enhances the Effect of Paclitaxel and Adriamycin in Human TNBC Cells
Triple-negative breast cancer (TNBC) has the poorest prognosis of all breast cancer subtypes. Recently, the activation of NF-κB, which is involved in the growth and survival of malignant tumors, has been demonstrated in TNBC, suggesting that NF-κB may serve as a new therapeutic target. In the presen...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9369077/ https://www.ncbi.nlm.nih.gov/pubmed/35955813 http://dx.doi.org/10.3390/ijms23158681 |
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author | Tsurushima, Katsumasa Tsubaki, Masanobu Takeda, Tomoya Matsuda, Takuya Kimura, Akihiro Takefuji, Honoka Okada, Akane Sakamoto, Chiaki Ishizaka, Toshihiko Nishida, Shozo |
author_facet | Tsurushima, Katsumasa Tsubaki, Masanobu Takeda, Tomoya Matsuda, Takuya Kimura, Akihiro Takefuji, Honoka Okada, Akane Sakamoto, Chiaki Ishizaka, Toshihiko Nishida, Shozo |
author_sort | Tsurushima, Katsumasa |
collection | PubMed |
description | Triple-negative breast cancer (TNBC) has the poorest prognosis of all breast cancer subtypes. Recently, the activation of NF-κB, which is involved in the growth and survival of malignant tumors, has been demonstrated in TNBC, suggesting that NF-κB may serve as a new therapeutic target. In the present study, we examined whether dimethyl fumarate (DMF), an NF-κB inhibitor, induces apoptosis in TNBC cells and enhances the apoptosis-inducing effect of paclitaxel and adriamycin. Cell survival was analyzed by the trypan blue assay and apoptosis assay. Protein detection was examined by immunoblotting. The activation of NF-κB p65 was correlated with poor prognosis in patients with TNBC. DMF induced apoptosis in MDA-MB-231 and BT-549 cells at concentrations that were non-cytotoxic to the normal mammary cell line MCF-10A. Furthermore, DMF inhibited NF-κB nuclear translocation and Survivin, XIAP, Bcl-xL, and Bcl-2 expression in MDA-MB-231 and BT-549 cells. Moreover, DMF enhanced the apoptosis-inducing effect of paclitaxel and adriamycin in MDA-MB-231 cells. These findings suggest that DMF may be an effective therapeutic agent for the treatment of TNBC, in which NF-κB is constitutively active. DMF may also be useful as an adjuvant therapy to conventional anticancer drugs. |
format | Online Article Text |
id | pubmed-9369077 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-93690772022-08-12 Dimethyl Fumarate Induces Apoptosis via Inhibition of NF-κB and Enhances the Effect of Paclitaxel and Adriamycin in Human TNBC Cells Tsurushima, Katsumasa Tsubaki, Masanobu Takeda, Tomoya Matsuda, Takuya Kimura, Akihiro Takefuji, Honoka Okada, Akane Sakamoto, Chiaki Ishizaka, Toshihiko Nishida, Shozo Int J Mol Sci Article Triple-negative breast cancer (TNBC) has the poorest prognosis of all breast cancer subtypes. Recently, the activation of NF-κB, which is involved in the growth and survival of malignant tumors, has been demonstrated in TNBC, suggesting that NF-κB may serve as a new therapeutic target. In the present study, we examined whether dimethyl fumarate (DMF), an NF-κB inhibitor, induces apoptosis in TNBC cells and enhances the apoptosis-inducing effect of paclitaxel and adriamycin. Cell survival was analyzed by the trypan blue assay and apoptosis assay. Protein detection was examined by immunoblotting. The activation of NF-κB p65 was correlated with poor prognosis in patients with TNBC. DMF induced apoptosis in MDA-MB-231 and BT-549 cells at concentrations that were non-cytotoxic to the normal mammary cell line MCF-10A. Furthermore, DMF inhibited NF-κB nuclear translocation and Survivin, XIAP, Bcl-xL, and Bcl-2 expression in MDA-MB-231 and BT-549 cells. Moreover, DMF enhanced the apoptosis-inducing effect of paclitaxel and adriamycin in MDA-MB-231 cells. These findings suggest that DMF may be an effective therapeutic agent for the treatment of TNBC, in which NF-κB is constitutively active. DMF may also be useful as an adjuvant therapy to conventional anticancer drugs. MDPI 2022-08-04 /pmc/articles/PMC9369077/ /pubmed/35955813 http://dx.doi.org/10.3390/ijms23158681 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Tsurushima, Katsumasa Tsubaki, Masanobu Takeda, Tomoya Matsuda, Takuya Kimura, Akihiro Takefuji, Honoka Okada, Akane Sakamoto, Chiaki Ishizaka, Toshihiko Nishida, Shozo Dimethyl Fumarate Induces Apoptosis via Inhibition of NF-κB and Enhances the Effect of Paclitaxel and Adriamycin in Human TNBC Cells |
title | Dimethyl Fumarate Induces Apoptosis via Inhibition of NF-κB and Enhances the Effect of Paclitaxel and Adriamycin in Human TNBC Cells |
title_full | Dimethyl Fumarate Induces Apoptosis via Inhibition of NF-κB and Enhances the Effect of Paclitaxel and Adriamycin in Human TNBC Cells |
title_fullStr | Dimethyl Fumarate Induces Apoptosis via Inhibition of NF-κB and Enhances the Effect of Paclitaxel and Adriamycin in Human TNBC Cells |
title_full_unstemmed | Dimethyl Fumarate Induces Apoptosis via Inhibition of NF-κB and Enhances the Effect of Paclitaxel and Adriamycin in Human TNBC Cells |
title_short | Dimethyl Fumarate Induces Apoptosis via Inhibition of NF-κB and Enhances the Effect of Paclitaxel and Adriamycin in Human TNBC Cells |
title_sort | dimethyl fumarate induces apoptosis via inhibition of nf-κb and enhances the effect of paclitaxel and adriamycin in human tnbc cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9369077/ https://www.ncbi.nlm.nih.gov/pubmed/35955813 http://dx.doi.org/10.3390/ijms23158681 |
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