Effect of Phlorotannins from Brown Algae Costaria costata on α-N-Acetylgalactosaminidase Produced by Duodenal Adenocarcinoma and Melanoma Cells
I. Yu. Bakunina, Т. И. Имбс, G. N. Likhatskaya, Valeria P. Grigorchuk, A. O. Zueva, Olesya S. Malyarenko, Svetlana P. Ermakova
Abstract
The inhibitor of human α-N-acetylgalactosaminidase (α-NaGalase) was isolated from a water–ethanol extract of the brown algae Costaria costata. Currently, tumor α-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 α-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 μg/mL, respectively. Molecular docking of the putative DP-15 oligophlorethol (P15OPh) and heptaphlorethol (PHPh) with human α-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 α-NaGalase of cancer cells and, therefore, has high therapeutic potential.