Cytotoxic and Metalloproteinase-inhibitory Effects of Ellagic Acid Against Oral Squamous Cell Carcinoma

Background/Aim: This study aimed to evaluate the in vitro antitumoral potential of different concentrations of ellagic acid against two oral squamous cell carcinoma (OSCC) cell lines with distinct tissue invasiveness profiles.

Materials and Methods: Normal keratinocytes (NOK) and OSCC cells CAL-27 and SCC-9 were treated with concentrations of EA from 5 to 662 μM for 24, 48 or 72 h. Cells were then submitted to viability analysis using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, and the secretion of metalloproteinases (MMP2 and MMP9) and TIMP metallopeptidase inhibitors (TIMP1 and TIMP2) were evaluated by enzyme-linked immunoassay. Data were submitted to analysis of variance, followed by Bonferroni’s test, considering 5% as the significance level.

Results: Ellagic acid was cytotoxic to OSCC cells for all exposures, rarely affecting viability of NOK cells, except for concentrations higher than 39 μM and after 72 h treatment. For OSCC cells, ellagic acid reduced MMP levels and increased TIMP2 expression after 48 or 72 h, while having no effect on these enzymes in normal cells throughout the exposure period.

Conclusion: Ellagic acid appeared to reduce cancer cell invasiveness in vitro, suggesting its potential as a promising therapeutic adjuvant for oral cancer, warranting further investigation.