Effect of Phlorotannins from Brown Algae <i>Costaria costata</i> on α-<i>N</i>-Acetylgalactosaminidase Produced by Duodenal Adenocarcinoma and Melanoma Cells
The inhibitor of human α-N-acetylgalactosaminidase (α-NaGalase) was isolated from a water–ethanol extract of the brown algae <i>Costaria costata</i>. Currently, tumor α-NaGalase is considered to be a therapeutic target in the treatment of cancer. According to NMR spectroscopy and mass sp...
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MDPI AG
2022-12-01
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| Series: | Marine Drugs |
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| author | Irina Bakunina Tatiana Imbs Galina Likhatskaya Valeria Grigorchuk Anastasya Zueva Olesya Malyarenko Svetlana Ermakova |
| author_facet | Irina Bakunina Tatiana Imbs Galina Likhatskaya Valeria Grigorchuk Anastasya Zueva Olesya Malyarenko Svetlana Ermakova |
| author_sort | Irina Bakunina |
| collection | DOAJ |
| description | The inhibitor of human α-N-acetylgalactosaminidase (α-NaGalase) was isolated from a water–ethanol extract of the brown algae <i>Costaria costata</i>. 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<sub>50</sub> 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. |
| first_indexed | 2024-03-09T11:52:43Z |
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| language | English |
| last_indexed | 2024-03-09T11:52:43Z |
| publishDate | 2022-12-01 |
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| series | Marine Drugs |
| spelling | doaj.art-a6d74d3d5625452995d3b0d7ce2237352023-11-30T23:13:34ZengMDPI AGMarine Drugs1660-33972022-12-012113310.3390/md21010033Effect of Phlorotannins from Brown Algae <i>Costaria costata</i> on α-<i>N</i>-Acetylgalactosaminidase Produced by Duodenal Adenocarcinoma and Melanoma CellsIrina Bakunina0Tatiana Imbs1Galina Likhatskaya2Valeria Grigorchuk3Anastasya Zueva4Olesya Malyarenko5Svetlana Ermakova6G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 159 Pr-t 100-let Vladivostoka Str., 690022 Vladivostok, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 159 Pr-t 100-let Vladivostoka Str., 690022 Vladivostok, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 159 Pr-t 100-let Vladivostoka Str., 690022 Vladivostok, RussiaFederal Scientific Center of the East Asia Terrestrial Biodiversity, Far Eastern Branch, Russian Academy of Sciences, 159 Pr-t 100-let Vladivostoka Str., 690022 Vladivostok, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 159 Pr-t 100-let Vladivostoka Str., 690022 Vladivostok, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 159 Pr-t 100-let Vladivostoka Str., 690022 Vladivostok, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, 159 Pr-t 100-let Vladivostoka Str., 690022 Vladivostok, RussiaThe inhibitor of human α-N-acetylgalactosaminidase (α-NaGalase) was isolated from a water–ethanol extract of the brown algae <i>Costaria costata</i>. 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<sub>50</sub> 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.https://www.mdpi.com/1660-3397/21/1/33α-N-acetylgalactosaminidaseα-NaGalaseinhibitorphlorotanninsbrown algae<i>Costaria costata</i> |
| spellingShingle | Irina Bakunina Tatiana Imbs Galina Likhatskaya Valeria Grigorchuk Anastasya Zueva Olesya Malyarenko Svetlana Ermakova Effect of Phlorotannins from Brown Algae <i>Costaria costata</i> on α-<i>N</i>-Acetylgalactosaminidase Produced by Duodenal Adenocarcinoma and Melanoma Cells Marine Drugs α-N-acetylgalactosaminidase α-NaGalase inhibitor phlorotannins brown algae <i>Costaria costata</i> |
| title | Effect of Phlorotannins from Brown Algae <i>Costaria costata</i> on α-<i>N</i>-Acetylgalactosaminidase Produced by Duodenal Adenocarcinoma and Melanoma Cells |
| title_full | Effect of Phlorotannins from Brown Algae <i>Costaria costata</i> on α-<i>N</i>-Acetylgalactosaminidase Produced by Duodenal Adenocarcinoma and Melanoma Cells |
| title_fullStr | Effect of Phlorotannins from Brown Algae <i>Costaria costata</i> on α-<i>N</i>-Acetylgalactosaminidase Produced by Duodenal Adenocarcinoma and Melanoma Cells |
| title_full_unstemmed | Effect of Phlorotannins from Brown Algae <i>Costaria costata</i> on α-<i>N</i>-Acetylgalactosaminidase Produced by Duodenal Adenocarcinoma and Melanoma Cells |
| title_short | Effect of Phlorotannins from Brown Algae <i>Costaria costata</i> on α-<i>N</i>-Acetylgalactosaminidase Produced by Duodenal Adenocarcinoma and Melanoma Cells |
| title_sort | effect of phlorotannins from brown algae i costaria costata i on α i n i acetylgalactosaminidase produced by duodenal adenocarcinoma and melanoma cells |
| topic | α-N-acetylgalactosaminidase α-NaGalase inhibitor phlorotannins brown algae <i>Costaria costata</i> |
| url | https://www.mdpi.com/1660-3397/21/1/33 |
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