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

• Published in: Marine drugs Vol. 21; no. 1; p. 33
• Main Authors: Bakunina, Irina, Imbs, Tatiana, Likhatskaya, Galina, Grigorchuk, Valeria, Zueva, Anastasya, Malyarenko, Olesya, Ermakova, Svetlana
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30-12-2022; MDPI
• Subjects: Adenocarcinoma; Algae; alpha-N-Acetylgalactosaminidase; Analytical methods; brown algae; Cancer; Carbon; Cells; Costaria costata; Cytotoxicity; Degree of polymerization; Enzymes; Ethanol; Glycoproteins; Humans; Hydrocarbons; inhibitor; Inhibitors; Magnetic resonance spectroscopy; Mass spectroscopy; Melanoma; Molecular docking; Molecular Docking Simulation; Molecular weight; NMR; NMR spectroscopy; Nuclear magnetic resonance; Ovarian cancer; Phaeophyceae; Phaeophyceae - chemistry; phlorotannins; Polymerization; Proteins; Spectrometry; Therapeutic targets; Tumors; α-N-acetylgalactosaminidase; α-NaGalase; α-N-acetylgalactosaminidase; inhibitor; carcinoma; melanoma; cancer cells; α-NaGalase; brown algae; phlorotannins; Costaria costata
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md21010033

The inhibitor of human α-N-acetylgalactosaminidase (α-NaGalase) was isolated from a water-ethanol extract of the brown algae
. 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 (IC
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.