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Antimetastatic activity and low systemic toxicity of tetradecyl gallate in a preclinical melanoma mouse model
Claudriana Locatelli1, Deborah Regina Carvalho, Alessandra Mascarello
1Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, SC, Brazil.
Abstract:
Gallates with eight or more carbon atoms in the lateral chain show potent anticancer activity against various cell lines. However, studies regarding the in vivo antimelanoma activity of tetradecyl gallate (C(14)) have not yet been reported. In this study an evaluation of the ability of C(14) to inhibit metastasis, using lung metastases as a model, was carried out. The experimental mouse melanoma model was established by intravenous injection of metastatic B16F10 melanoma cells. The systemic toxicity of C(14) was evaluated in vivo by monitoring the weight, survival, biochemical and hematological parameters, and through histological analysis. It was observed that C(14) decreased lung metastasis in vivo by 80% and increased the survival rate of the animals without toxic effects. Additionally, C(14) induced cytotoxic effects on B16F10 cells, inhibited the inter-cellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expression, and significantly decreased cell adhesion. These results reveal that C(14) has potent antimetastatic ability and is a good candidate for further study as a potential therapeutic agent for tumor metastases.
Insights
Tetradecyl gallate (C14) significantly reduced melanoma lung metastasis by 80% in mice. This compound demonstrated potent antimetastatic effects without causing toxic side effects, showing promise for cancer therapy.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Gallates with longer lateral chains exhibit anticancer properties.
- Tetradecyl gallate (C14) has not been previously studied for its in vivo antimelanoma effects.
- Melanoma metastasis remains a significant challenge in cancer treatment.
Purpose of the Study:
- To evaluate the in vivo antimetastatic activity of tetradecyl gallate (C14) against melanoma.
- To assess the systemic toxicity of C14 in a mouse model.
- To investigate the mechanisms underlying C14's antimetastatic effects.
Main Methods:
- An experimental mouse melanoma model was established using intravenous injection of B16F10 melanoma cells.
- Systemic toxicity was assessed through weight, survival, biochemical, hematological, and histological analyses.
- Inhibition of metastasis, cell adhesion molecules (ICAM-1, VCAM-1), and cell adhesion were measured.
Main Results:
- C14 decreased lung metastasis by 80% and increased animal survival rates without observable toxicity.
- C14 exhibited cytotoxic effects on B16F10 melanoma cells in vitro.
- C14 inhibited ICAM-1 and VCAM-1 expression and reduced melanoma cell adhesion.
Conclusions:
- Tetradecyl gallate (C14) possesses significant in vivo antimetastatic potential against melanoma.
- C14 demonstrates a favorable safety profile, indicating its potential as a therapeutic agent.
- Further research into C14 as a treatment for tumor metastasis is warranted.
