Berberine hydrochloride induces apoptosis in triple-negative breast cancer cells through modulation of the
Zhimin Zhao1,2, Shu Xu1,2, Yushi Yang2
1School of Clinical Medicine, Guizhou Medical University, Guiyang, China.
Abstract:
1. Triple-negative breast cancer (TNBC) is a highly aggressive subtype with few available therapeutic strategies. Berberine Hydrochloride (BBR) has shown anticancer potential but its mechanisms in TNBC remain unclear.
Abstract:
2. We used cell viability assays, immunohistochemistry, western blotting, and metabolic assays to investigate the effects of BBR on TNBC cells.
Abstract:
3. BBR markedly reduced the viability of TNBC cell lines and increased apoptosis compared with untreated controls. Relative to adjacent non-tumor tissues, TNBC tumor samples showed higher levels of total p65, p65 K310 acetylation, and p65 S536 phosphorylation; the same pattern appeared in TNBC cell lines compared with normal breast epithelial cells. In TNBC cells, both BBR and NAM increased p65 K310 acetylation while reducing S536 phosphorylation relative to vehicle treatment. SIRT2 expression was elevated in TNBC tumors and cell lines compared with their controls, whereas BBR decreased SIRT2 levels. BBR also induced stronger oxidative stress than controls and caused mitochondrial dysfunction, including membrane potential loss and reduced oxygen consumption and acidification rates.
Abstract:
4. BBR induces apoptosis in TNBC cells and is associated with p65 acetylation/phosphorylation changes, SIRT2 downregulation, and mitochondrial dysfunction. This study provides a novel mechanistic basis for BBR as a potential therapeutic agent for TNBC.
Insights
Berberine Hydrochloride (BBR) effectively reduces triple-negative breast cancer (TNBC) cell viability and induces apoptosis. This study reveals BBR
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options.
- Berberine Hydrochloride (BBR) exhibits anticancer properties, but its specific mechanisms in TNBC are not well understood.
Purpose of the Study:
- To investigate the molecular mechanisms underlying the effects of BBR on TNBC cells.
- To explore BBR's potential as a therapeutic agent for TNBC.
Main Methods:
- Cell viability assays were performed to assess BBR's impact on TNBC cell survival.
- Immunohistochemistry, western blotting, and metabolic assays were utilized to analyze molecular changes.
- Apoptosis, protein modifications (acetylation, phosphorylation), SIRT2 expression, and mitochondrial function were evaluated.
Main Results:
- BBR significantly decreased TNBC cell viability and promoted apoptosis.
- BBR modulated p65 acetylation and phosphorylation, downregulated SIRT2 expression, and induced oxidative stress.
- Mitochondrial dysfunction, including membrane potential loss and reduced metabolic rates, was observed.
Conclusions:
- BBR induces apoptosis in TNBC cells through mechanisms involving p65 pathway modulation, SIRT2 downregulation, and mitochondrial dysfunction.
- These findings establish a novel mechanistic foundation for BBR's therapeutic potential in treating triple-negative breast cancer.
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