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Vol 59, No 4 (2021)
Original paper
Submitted: 2021-08-13
Accepted: 2021-12-02
Published online: 2021-12-09
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Soyasaponin Ag inhibits triple-negative breast cancer progression via targeting the DUSP6/MAPK signaling

Shoucheng Huang1, Ping Huang2, Huazhang Wu3, Song Wang1, Guodong Liu1
·
Pubmed: 34970732
·
Folia Histochem Cytobiol 2021;59(4):291-301.
Affiliations
  1. College of Life and Health Science, Anhui Science and Technology University, Fengyang 233100, Anhui, China
  2. College of Chemical and Materials Engineering, Anhui Science and Technology University, Fengyang 233100, Anhui, China
  3. School of Life Science, Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Bengbu 233030, Anhui, China

open access

Vol 59, No 4 (2021)
ORIGINAL PAPERS
Submitted: 2021-08-13
Accepted: 2021-12-02
Published online: 2021-12-09

Abstract

Introduction. Soyasaponins are triterpenoid glycosides discovered in soybean and have anti-cancer properties. Soyasaponin A was reported to repress estrogen-insensitive breast cancer cell proliferation. This study intends to explore the role of one isomer of soyasaponin A, i.e. soyasaponin Ag (Ssa Ag), in triple-negative breast cancer (TNBC) development.

Material and methods. Bioinformatic databases were used to predict DUSP6 expression in breast cancer (BC) as well as the correlation between the expression of DUSP6 (or MAPK1, MAPK14) with the prognosis of patients with BC. The expression of DUSP6/MAPK signaling-related genes (DUSP6, MAPK1, and MAPK14) in TNBC cell lines was assessed via Western blot analysis and RT-qPCR. Levels of cell apoptosis proteins (Bax and Bcl-2) in TNBC cells were assessed via Western blot analysis. CCK-8 assay, colony formation assay, and flow cytometry analysis were conducted for the measurement of TNBC cell growth and apoptosis. In vivo xenograft assay was employed for investigating the biological influence of Ssa Ag on tumor growth.

Results. The poor prognosis of BC patients was linked to the aberrant expression of DUSP6/MAPK pathway
genes. Low expression of DUSP6 or high expression of MAPK1 (or MAPK14) was correlated to poor prognosis. DUSP6 was downregulated while MAPK1 and MAPK14 were upregulated in TNBC cells versus normal cells. Ssa Ag upregulated DUSP6 expression while downregulated MAPK1 and MAPK14 expression, inhibiting the MAPK signaling pathway. Additionally, Ssa Ag promoted in vitro TNBC cell apoptosis and restrained cell growth, and repressed in vivo tumor growth.

Conclusions. Ssa Ag inhibited TNBC progression via upregulating DUSP6 and inactivating the MAPK signaling pathway.

Abstract

Introduction. Soyasaponins are triterpenoid glycosides discovered in soybean and have anti-cancer properties. Soyasaponin A was reported to repress estrogen-insensitive breast cancer cell proliferation. This study intends to explore the role of one isomer of soyasaponin A, i.e. soyasaponin Ag (Ssa Ag), in triple-negative breast cancer (TNBC) development.

Material and methods. Bioinformatic databases were used to predict DUSP6 expression in breast cancer (BC) as well as the correlation between the expression of DUSP6 (or MAPK1, MAPK14) with the prognosis of patients with BC. The expression of DUSP6/MAPK signaling-related genes (DUSP6, MAPK1, and MAPK14) in TNBC cell lines was assessed via Western blot analysis and RT-qPCR. Levels of cell apoptosis proteins (Bax and Bcl-2) in TNBC cells were assessed via Western blot analysis. CCK-8 assay, colony formation assay, and flow cytometry analysis were conducted for the measurement of TNBC cell growth and apoptosis. In vivo xenograft assay was employed for investigating the biological influence of Ssa Ag on tumor growth.

Results. The poor prognosis of BC patients was linked to the aberrant expression of DUSP6/MAPK pathway
genes. Low expression of DUSP6 or high expression of MAPK1 (or MAPK14) was correlated to poor prognosis. DUSP6 was downregulated while MAPK1 and MAPK14 were upregulated in TNBC cells versus normal cells. Ssa Ag upregulated DUSP6 expression while downregulated MAPK1 and MAPK14 expression, inhibiting the MAPK signaling pathway. Additionally, Ssa Ag promoted in vitro TNBC cell apoptosis and restrained cell growth, and repressed in vivo tumor growth.

Conclusions. Ssa Ag inhibited TNBC progression via upregulating DUSP6 and inactivating the MAPK signaling pathway.

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Keywords

soyasaponin Ag; DUSP6/MAPK signaling; triple-negative breast cancer; proliferation; apoptosis

About this article
Title

Soyasaponin Ag inhibits triple-negative breast cancer progression via targeting the DUSP6/MAPK signaling

Journal

Folia Histochemica et Cytobiologica

Issue

Vol 59, No 4 (2021)

Article type

Original paper

Pages

291-301

Published online

2021-12-09

Page views

6534

Article views/downloads

628

DOI

10.5603/FHC.a2021.0029

Pubmed

34970732

Bibliographic record

Folia Histochem Cytobiol 2021;59(4):291-301.

Keywords

soyasaponin Ag
DUSP6/MAPK signaling
triple-negative breast cancer
proliferation
apoptosis

Authors

Shoucheng Huang
Ping Huang
Huazhang Wu
Song Wang
Guodong Liu

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