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13-Butoxyberberine Bromide Inhibits Migration and Invasion in Skin Cancer A431 Cells
Phuriwat Laomethakorn1, Malatee Tayeh2,3, Siritron Samosorn4
1Department of Biochemistry, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Thailand.
Abstract:
Cancer metastasis is the primary cause of cancer morbidity and mortality. Anti-metastasis mechanism of skin cancer by 13-butoxyberberine bromide, a novel berberine derivative, has not yet been reported. This study investigated the effects of 13-butoxyberberine bromide on migration and invasion of skin cancer A431 cells. The cytotoxicity of 13-butoxyberberine bromide was determined by MTT assay. The effect of 13-butoxyberberine bromide on cell migration and invasion were examined using a wound-healing assay, transwell migration assay, and transwell invasion assay, respectively. The cell adhesion ability was determined by an adhesion assay. Protein expressions that play important roles in cancer migration and invasion were evaluated by Western blot analysis. The results showed that 13-butoxyberberine bromide effectively inhibited cell migration, invasion, and adhesion in A431 cells. Interestingly, 13-butoxyberberine bromide was more effective for cell migration inhibition than berberine. In addition, 13-butoxyberberine bromide showed anti-migration and anti-invasion effects by down-regulated MMP-2 and MMP-9 expression and up-regulated TIMP-1 and TIMP-2 expression in A431 cells. Moreover, pretreatment with 13-butoxyberberine bromide significantly inhibited EGF-induced cell migration and p-EGFR, ERK, p-ERK, STAT3, and p-STAT3 expressions in A431 cells at lower concentrations when compared with the berberine. These findings indicated that 13-butoxyberberine bromide could be further developed as an anticancer agent.
Insights
13-butoxyberberine bromide, a novel berberine derivative, effectively inhibits skin cancer cell migration, invasion, and adhesion. This compound shows greater anti-metastasis potential than berberine, suggesting its development as an anticancer agent.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Cancer metastasis is a leading cause of cancer mortality.
- The anti-metastasis mechanisms of novel berberine derivatives, such as 13-butoxyberberine bromide, remain largely unexplored in skin cancer.
- Understanding these mechanisms is crucial for developing new therapeutic strategies.
Purpose of the Study:
- To investigate the anti-metastasis effects of 13-butoxyberberine bromide on A431 skin cancer cells.
- To elucidate the molecular mechanisms underlying its anti-migratory and anti-invasive properties.
- To compare its efficacy with the parent compound, berberine.
Main Methods:
- Cytotoxicity was assessed using MTT assays.
- Cell migration, invasion, and adhesion were evaluated through wound-healing, Transwell migration, and Transwell invasion assays.
- Protein expression levels of key regulators (MMP-2, MMP-9, TIMP-1, TIMP-2, EGFR, ERK, STAT3) were analyzed via Western blotting.
Main Results:
- 13-butoxyberberine bromide significantly inhibited A431 cell migration, invasion, and adhesion.
- The compound demonstrated superior anti-migratory effects compared to berberine.
- It modulated the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), and suppressed EGF-induced signaling pathways (EGFR, ERK, STAT3).
Conclusions:
- 13-butoxyberberine bromide exhibits potent anti-metastasis activity against skin cancer cells.
- Its mechanism involves the downregulation of MMPs and upregulation of TIMPs, as well as inhibition of key signaling pathways.
- 13-butoxyberberine bromide holds promise as a potential anticancer therapeutic agent.
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