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Gene Expression Profiles Modulated by Lipophilic Sea Buckthorn (Hippophae rhamnoides L.) Extract in BT-549
Simona Visan1,2, Loredana Balacescu1, Flaviu Drigla1
1Department of Genetics, Genomics, and Experimental Pathology The Oncology Institute "Professor Dr. Ion Chiricuta" Cluj-Napoca Romania.
Abstract:
Triple-negative breast cancer (TNBC) is an aggressive subtype with high heterogeneity, metastasis, and drug resistance, underscoring the need for new therapeutic strategies. Sea buckthorn berries, long used in traditional medicine, are rich in carotenoids with reported anticancer activity. To investigate their transcriptional effects, we treated BT-549 TNBC cells with a saponified lipophilic sea buckthorn berry extract (LSBE) and performed gene expression profiling using microarray (four independent replicates of treated, respectively, untreated cells). LSBE altered the expression of 330 protein-coding genes (111 downregulated, 219 upregulated; fold ratio ±1.5, adj. p < 0.05). ingenuity pathway analysis (IPA) revealed activation of cholesterol biosynthesis (z = 3.46, p = 2.7E-15) and ferroptosis (z = 0.78, p = 5.3E-09), while oxidative stress (z = -2.18, p = 3.4E-05) and cholesterol accumulation (z = -2.14, p = 3.4E-06) were inhibited. Gene set enrichment analysis (GSEA) further indicated upregulation of cholesterol homeostasis and mTORC1 signaling. Our findings suggest that carotenoid-enriched LSBE modulates key pathways related to cellular homeostasis, antioxidant defense, and apoptosis in TNBC. While limited to transcriptional profiling, this exploratory study provides a foundation for future functional validation of LSBE as a complementary TNBC therapeutic approach.
Insights
Sea buckthorn berry extract (LSBE) impacts gene expression in triple-negative breast cancer (TNBC) cells, activating cholesterol biosynthesis and ferroptosis pathways. This suggests LSBE
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Triple-negative breast cancer (TNBC) is aggressive, heterogeneous, and resistant to therapies, necessitating novel treatment strategies.
- Sea buckthorn berries contain carotenoids with potential anticancer properties, warranting investigation into their molecular mechanisms.
Purpose of the Study:
- To investigate the transcriptional effects of a saponified lipophilic sea buckthorn berry extract (LSBE) on BT-549 TNBC cells.
- To identify key biological pathways modulated by LSBE in TNBC cells.
Main Methods:
- Gene expression profiling using microarray analysis on LSBE-treated and untreated BT-549 TNBC cells (four replicates each).
- Ingenuity Pathway Analysis (IPA) and Gene Set Enrichment Analysis (GSEA) to interpret gene expression data.
Main Results:
- LSBE altered the expression of 330 protein-coding genes (111 downregulated, 219 upregulated).
- IPA revealed activation of cholesterol biosynthesis and ferroptosis pathways.
- Inhibition of oxidative stress and cholesterol accumulation pathways was observed.
- GSEA indicated upregulation of cholesterol homeostasis and mTORC1 signaling.
Conclusions:
- LSBE modulates critical pathways including cholesterol metabolism, cellular homeostasis, antioxidant defense, and apoptosis in TNBC cells.
- This study provides a transcriptional basis for exploring LSBE as a complementary therapeutic agent for TNBC.
- Further functional studies are needed to validate these findings.
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