Effect of Phlorotannins from Brown Algae <i>Costaria costata</i> on α-<i>N</i>-Acetylgalactosaminidase Produced by Duodenal Adenocarcinoma and Melanoma Cells
Irina Bakunina,
Tatiana Imbs,
Galina Likhatskaya,
Valeria Grigorchuk,
Anastasya Zueva,
Olesya Malyarenko,
Svetlana Ermakova
Affiliations
Irina Bakunina
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 159 Pr-t 100-let Vladivostoka Str., 690022 Vladivostok, Russia
Tatiana Imbs
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 159 Pr-t 100-let Vladivostoka Str., 690022 Vladivostok, Russia
Galina Likhatskaya
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 159 Pr-t 100-let Vladivostoka Str., 690022 Vladivostok, Russia
Valeria Grigorchuk
Federal Scientific Center of the East Asia Terrestrial Biodiversity, Far Eastern Branch, Russian Academy of Sciences, 159 Pr-t 100-let Vladivostoka Str., 690022 Vladivostok, Russia
Anastasya Zueva
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 159 Pr-t 100-let Vladivostoka Str., 690022 Vladivostok, Russia
Olesya Malyarenko
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 159 Pr-t 100-let Vladivostoka Str., 690022 Vladivostok, Russia
Svetlana Ermakova
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 159 Pr-t 100-let Vladivostoka Str., 690022 Vladivostok, Russia
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.
