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Erucin Targets Oncogenic Signaling Pathways in Triple-Negative Breast Cancer: An Integrated Network Pharmacology and
Humera Banu1, Eyad Al Shammari1, Husam Qanash2,3
1Department of Clinical Nutrition, College of Applied Medical Sciences, University of Ha'il, Ha'il P.O. Box 2440, Saudi Arabia.
Abstract:
This study aims to investigate the potential anticancer effects of erucin, an isothiocyanate derived from Eruca sativa, in triple-negative breast cancer (TNBC) by predicting molecular targets and evaluating its in vitro effects on TNBC cell proliferation, apoptosis and cell cycle distribution. Potential protein targets of erucin were identified using SwissTargetPrediction, resulting in 117 targets, of which 84 overlapped with TNBC-related genes sourced from GeneCards, DisGeNET, and OMIM. Protein-protein interaction analysis was performed to identify key hub genes. In vitro experiments were conducted using MDA-MB-231 TNBC cells to assess dose-dependent effects on cell viability. Flow cytometry was employed to evaluate apoptotic cell populations and cell cycle distribution. Protein-protein interaction analysis identified ten hub genes, including AKT1, STAT3, EGFR, and MMP9, representing highly connected nodes within the predicted interaction network. In vitro studies showed dose-dependent reduction in MDA-MB-231 cell viability following erucin treatment, with an IC50 of approximately 48.87 µg/mL. Flow cytometry revealed increased apoptotic cell population and G1 phase accumulation. These findings suggest that erucin is associated with cytotoxic and antiproliferative effects in TNBC cells and may interact with multiple cancer-related targets. However, the identified molecular targets and pathways are based on computational predictions and require further experimental validation. Overall, this study provides a preliminary integrated framework linking computational predictions with experimental observations, which may support future mechanistic and preclinical investigations of erucin in TNBC.
Insights
Erucin, a compound from Eruca sativa, shows anticancer potential against triple-negative breast cancer (TNBC). It reduced cancer cell viability and induced apoptosis in vitro, suggesting it may target key cancer-related genes.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Triple-negative breast cancer (TNBC) presents a significant therapeutic challenge due to its aggressive nature and limited targeted treatment options.
- Isothiocyanates, such as erucin derived from Eruca sativa, are being explored for their potential anticancer properties.
- Understanding the molecular mechanisms and targets of natural compounds is crucial for developing novel cancer therapies.
Purpose of the Study:
- To investigate the anticancer effects of erucin in triple-negative breast cancer (TNBC).
- To predict potential molecular targets of erucin using computational methods.
- To evaluate the in vitro effects of erucin on TNBC cell proliferation, apoptosis, and cell cycle distribution.
Main Methods:
- Computational target prediction using SwissTargetPrediction, integrated with TNBC gene databases (GeneCards, DisGeNET, OMIM).
- Protein-protein interaction network analysis to identify key hub genes.
- In vitro assays using MDA-MB-231 TNBC cells to assess cell viability, apoptosis, and cell cycle distribution via flow cytometry.
Main Results:
- Erucin demonstrated a dose-dependent reduction in MDA-MB-231 cell viability with an IC50 of approximately 48.87 µg/mL.
- Flow cytometry analysis indicated an increase in apoptotic cell populations and G1 phase cell cycle arrest following erucin treatment.
- Computational analysis identified several potential molecular targets and ten key hub genes (e.g., AKT1, STAT3, EGFR, MMP9) involved in TNBC.
Conclusions:
- Erucin exhibits cytotoxic and antiproliferative effects on TNBC cells, suggesting therapeutic potential.
- The study provides a preliminary framework linking computational predictions with experimental findings for erucin in TNBC.
- Further experimental validation of identified molecular targets and pathways is warranted for future mechanistic and preclinical studies.
