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

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options and poor prognosis.
• Identifying novel therapeutic targets is crucial for improving TNBC patient outcomes.
• High relapse rates underscore the urgent need for effective TNBC therapies.

Purpose of the Study:

• To identify potential drug candidates for triple-negative breast cancer (TNBC) treatment using drug repositioning.
• To evaluate the efficacy of candidate compounds in inhibiting TNBC cell proliferation and metastasis.
• To elucidate the molecular mechanisms underlying the anti-cancer effects of identified compounds.

Main Methods:

• Transcriptional signature analysis of TNBC using Gene Expression Omnibus (GEO) and Connectivity Map (CMap) for drug repositioning.
• In vitro assays including CCK8, colony formation, Transwell, and wound healing to assess proliferation and metastasis.
• Proteomic analysis and Drug Affinity Responsive Target Stability (DARTS) coupled with LC-MS/MS to explore molecular mechanisms and drug targets.

Main Results:

• Eugenol demonstrated significant inhibition of TNBC cell proliferation and metastasis in vitro.
• Proteomic analysis indicated that eugenol acts via the NOD1-NF-κB signaling pathway.
• DARTS experiments suggested that eugenol may directly bind to NF-κB in TNBC cells.

Conclusions:

• Eugenol emerges as a potential therapeutic agent for triple-negative breast cancer (TNBC).
• The findings highlight the NOD1-NF-κB pathway as a key target for eugenol's anti-TNBC activity.
• Further investigation into eugenol as a TNBC treatment is warranted.