Eugenol modulates the NOD1-NF-κB signaling pathway via targeting NF-κB protein in triple-negative breast cancer cells

Xiaoyu Shi; Weiwei Zhang; Xiao Bao; Xiaozhu Liu; Ming Yang; Chengliang Yin

doi:10.3389/fendo.2023.1136067

Eugenol modulates the NOD1-NF-κB signaling pathway via targeting NF-κB protein in triple-negative breast cancer cells

Front Endocrinol (Lausanne). 2023 Feb 27:14:1136067. doi: 10.3389/fendo.2023.1136067. eCollection 2023.

Authors

Xiaoyu Shi¹, Weiwei Zhang¹, Xiao Bao², Xiaozhu Liu³, Ming Yang⁴, Chengliang Yin⁵

Affiliations

¹ Department of Pharmacy, Yantai University, Yantai, China.
² Pharmacy Department, Wenzhou Nursing School, Wenzhou, China.
³ Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
⁴ Obstetrics Department, The First Dongguan Affiliated Hospital of Guangdong Medical University, Dongguan, China.
⁵ Macau University of Science and Technology, Faculty of Medicine, Macau, Macau SAR, China.

Abstract

Background: The most aggressive subtype of breast cancer, triple-negative breast cancer (TNBC), has a worse prognosis and a higher probability of relapse since there is a narrow range of treatment options. Identifying and testing potential therapeutic targets for the treatment of TNBC is of high priority.

Methods: Using a transcriptional signature of triple-negative breast cancer collected from Gene Expression Omnibus (GEO), CMap was utilized to reposition compounds for the treatment of TNBC. CCK8 and colony formation experiments were performed to detect the effect of the candidate drug on the proliferation of TNBC cells. Meanwhile, transwell and wound healing assay were implemented to detect cell metastasis change caused by the candidate drug. Moreover, the proteomic approach was presently ongoing to evaluate the underlying mechanism of the candidate drug in TNBC. Furthermore, drug affinity responsive target stability (DARTS) coupled with LC-MS/MS was carried out to explore the potential drug target candidate in TNBC cells.

Results: We found that the most widely used medication, eugenol, reduced the growth and metastasis of TNBC cells. According to the underlying mechanism revealed by proteomics, eugenol could inhibit TNBC cell proliferation and metastasis via the NOD1-NF-κB signaling pathway. DARTS experiment further revealed that eugenol may bind to NF-κB in TNBC cells.

Concludes: Our findings pointed out that eugenol was a potential candidate drug for the treatment of TNBC.

Keywords: CMAP; DARTS; eugenol; proteomics; target protein; triple-negative breast cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Chromatography, Liquid
Eugenol / pharmacology
Eugenol / therapeutic use
Humans
NF-kappa B* / metabolism
Neoplasm Recurrence, Local
Nod1 Signaling Adaptor Protein / metabolism
Nod1 Signaling Adaptor Protein / pharmacology
Proteomics
Signal Transduction
Tandem Mass Spectrometry
Triple Negative Breast Neoplasms* / drug therapy
Triple Negative Breast Neoplasms* / genetics
Triple Negative Breast Neoplasms* / pathology

Substances

NF-kappa B
Eugenol
NOD1 protein, human
Nod1 Signaling Adaptor Protein

Grants and funding

This work is supported by the grants from Project of schools directly under the Wenzhou Municipal Bureau (WX2022056), Dongguan Science and Technology of Social Development Program (202050715032200).