Effect of Phlorotannins from Brown Algae Costaria costata on -N-Acetylgalactosaminidase Produced by Duodenal Adenocarcinoma and Melanoma Cells

The inhibitor of human alpha-N-acetylgalactosaminidase (alpha-NaGalase) was isolated from a water-ethanol extract of the brown algae Costaria costata. Currently, tumor alpha-NaGalase is considered to be a therapeutic target in the treatment of cancer. According to NMR spectroscopy and mass spectrometric analysis, it is a high-molecular-weight fraction of phlorethols with a degree of polymerization (DP) equaling 11-23 phloroglucinols (CcPh). It was shown that CcPh is a direct inhibitor of alpha-NaGalases isolated from HuTu 80 and SK-MEL-28 cells (IC50 0.14 +/- 0.008 and 0.12 +/- 0.004 mg/mL, respectively) and reduces the activity of this enzyme in HuTu 80 and SK-MEL-28 cells up to 50% at concentrations of 15.2 +/- 9.5 and 5.7 +/- 1.6 mu g/mL, respectively. Molecular docking of the putative DP-15 oligophlorethol (P15OPh) and heptaphlorethol (PHPh) with human alpha-NaGalase (PDB ID 4DO4) showed that this compound forms a complex and interacts directly with the Asp 156 and Asp 217 catalytic residues of the enzyme in question. Thus, brown algae phlorethol CcPh is an effective marine-based natural inhibitor of the alpha-NaGalase of cancer cells and, therefore, has high therapeutic potential.