Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Tsurushima, Katsumasa, Tsubaki, Masanobu, Takeda, Tomoya, Matsuda, Takuya, Kimura, Akihiro, Takefuji, Honoka, Okada, Akane, Sakamoto, Chiaki, Ishizaka, Toshihiko, Nishida, Shozo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784766347475943424
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
work_keys_str_mv AT tsurushimakatsumasa dimethylfumarateinducesapoptosisviainhibitionofnfkbandenhancestheeffectofpaclitaxelandadriamycininhumantnbccells
AT tsubakimasanobu dimethylfumarateinducesapoptosisviainhibitionofnfkbandenhancestheeffectofpaclitaxelandadriamycininhumantnbccells
AT takedatomoya dimethylfumarateinducesapoptosisviainhibitionofnfkbandenhancestheeffectofpaclitaxelandadriamycininhumantnbccells
AT matsudatakuya dimethylfumarateinducesapoptosisviainhibitionofnfkbandenhancestheeffectofpaclitaxelandadriamycininhumantnbccells
AT kimuraakihiro dimethylfumarateinducesapoptosisviainhibitionofnfkbandenhancestheeffectofpaclitaxelandadriamycininhumantnbccells
AT takefujihonoka dimethylfumarateinducesapoptosisviainhibitionofnfkbandenhancestheeffectofpaclitaxelandadriamycininhumantnbccells
AT okadaakane dimethylfumarateinducesapoptosisviainhibitionofnfkbandenhancestheeffectofpaclitaxelandadriamycininhumantnbccells
AT sakamotochiaki dimethylfumarateinducesapoptosisviainhibitionofnfkbandenhancestheeffectofpaclitaxelandadriamycininhumantnbccells
AT ishizakatoshihiko dimethylfumarateinducesapoptosisviainhibitionofnfkbandenhancestheeffectofpaclitaxelandadriamycininhumantnbccells
AT nishidashozo dimethylfumarateinducesapoptosisviainhibitionofnfkbandenhancestheeffectofpaclitaxelandadriamycininhumantnbccells