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Published on: June 13, 2014
Comprehensive Evaluation of Usnic Acid as a Potential Drug Candidate for Triple-Negative Breast Cancer: Insights from
Ümmügülsüm Tanman1, Mehmet Kürşat Derici2, Mine Türktaş3
1Biotechnology Institute, Ankara University, Ankara 06135, Türkiye.
Background:
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited treatment options, prompting extensive research into novel therapeutics. This study presents a comprehensive molecular characterization of usnic acid in TNBC using transcriptomic, proteomic, and in vivo analyses.
Results:
Transcriptome profiling identified 974 differentially expressed genes (201 upregulated, 773 downregulated; p ≤ 0.05, FC ≥ 2) between control and usnic acid-treated MDA-MB-231 cells, while 4956 DEGs were detected between usnic acid-treated normal epithelial and TNBC cells. Proteomic analysis revealed significant changes in 372 proteins (50 upregulated and 322 downregulated). Functional enrichment analyses indicated that usnic acid modulates key oncogenic pathways, including gonadotropin, CCKR, integrin-ECM signaling, and lipid/energy metabolism. Flow cytometry confirmed increased apoptosis, evidenced by upregulation of pro-apoptotic genes and suppression of anti-apoptotic genes. In vivo xenograft models further validated the tumor-suppressive effects of usnic acid.
Conclusions:
In light of the findings, this study constitutes the first comprehensive integrated transcriptomic and proteomic evaluation of usnic acid in TNBC, supported by functional and in vivo validation. Collectively, the results position usnic acid as a compelling therapeutic candidate that has successfully passed key in vitro and in vivo preclinical evaluations, warranting further investigation in advanced preclinical models and potential translation toward clinical development for TNBC.
Insights
Usnic acid shows promise as a novel therapeutic for triple-negative breast cancer (TNBC). This study demonstrates its tumor-suppressive effects through molecular characterization and in vivo validation, supporting further clinical development.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options.
- Research is ongoing for novel treatments for TNBC.
- Usnic acid is investigated for its potential in TNBC therapy.
Purpose of the Study:
- To comprehensively characterize the molecular effects of usnic acid in TNBC.
- To evaluate usnic acid's therapeutic potential using transcriptomic, proteomic, and in vivo analyses.
- To validate usnic acid's efficacy in preclinical TNBC models.
Main Methods:
- Transcriptome and proteomic profiling of usnic acid-treated TNBC cells.
- Functional enrichment analysis of modulated oncogenic pathways.
- In vivo xenograft models to assess tumor-suppressive effects.
- Flow cytometry to confirm apoptosis induction.
Main Results:
- Usnic acid significantly altered gene expression (974 DEGs) and protein levels (372 proteins) in TNBC cells.
- Modulation of key oncogenic pathways including gonadotropin and integrin-ECM signaling.
- Demonstrated increased apoptosis and validated tumor-suppressive effects in vivo.
Conclusions:
- This study provides the first integrated transcriptomic and proteomic evaluation of usnic acid in TNBC.
- Usnic acid exhibits significant therapeutic potential, passing in vitro and in vivo preclinical evaluations.
- Usnic acid warrants further investigation for clinical development in TNBC treatment.
