Antimetastatic activity and low systemic toxicity of tetradecyl gallate in a preclinical melanoma mouse model

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.

Antiproliferative and Uncoupling Effects of Delocalized, Lipophilic, Cationic Gallic Acid Derivatives on Cancer Cell Lines. Validation in Vivo in Singenic Mice

“…Interestingly, a preclinical study performed with tetradecyl gallate reported a decrease in tumor size and metastasis of melanoma in an animal model. According to the authors, this effect was attributed to the inhibition of GSH synthesis and to the depletion of ATP, with no apparent signs of toxicity . Therefore, further experiments are under way to evaluate the toxicity and effectiveness of these compounds as potential antineoplastic cancer agents …”

Gallic acid downregulates matrix metalloproteinase‐2 (MMP‐2) and MMP‐9 in human leukemia cells with expressed Bcr/Abl

“…Noticeably, gallic acid is reported to be toxic to human microvascular endothelia cell culture when the gallic acid concentration used is higher than 10 μM . Recent studies reveal that 100 μM tetradecyl gallate increases effectively the survival rate of preclinical melanoma mouse model through reducing lung metastasis in vivo, but show low systemic toxicity in the animals . Thus, gallic acid derivatives should be a good candidate for additional evaluation as a potential therapeutic agent for reducing or treating hemotologic malignances.…”

Gallic Acid and Dodecyl Gallate Prevents Carbon Tetrachloride-Induced Acute and Chronic Hepatotoxicity by Enhancing Hepatic Antioxidant Status and Increasing p53 Expression

“…10,13,[45][46][47] The results of this study suggest that GA and DGA present a hepatoprotective effect against the toxic action promoted by CCl 4 . The results of Table 5 indicate that the effect of GA seems to be dose dependent, while the effect of the DGA is dose-independent.…”

“…However, they show changes in these markers when given in animals with tumors or in tumor cells. 10,13,[45][46][47] These results lead us to believe that gallic acid and its derivatives selectively act on damaged cells and tissues.…”