MDPI - Publisher of Open Access Journals

18 pages, 3108 KiB

Open AccessArticle

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

by Irina Bakunina, Tatiana Imbs, Galina Likhatskaya, Valeria Grigorchuk, Anastasya Zueva, Olesya Malyarenko and Svetlana Ermakova

Mar. Drugs 2023, 21(1), 33; https://doi.org/10.3390/md21010033 - 30 Dec 2022

Cited by 7 | Viewed by 2381

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. Full article

(This article belongs to the Special Issue Enzyme Inhibitors from Marine Resources)

► Show Figures

Figure 1

17 pages, 4334 KiB

Open AccessArticle

Effects of Sponge-Derived Alkaloids on Activities of the Bacterial α-D-Galactosidase and Human Cancer Cell α-N-Acetylgalactosaminidase

by Natalia Utkina, Galina Likhatskaya, Olesya Malyarenko, Svetlana Ermakova, Larisa Balabanova, Lubov Slepchenko and Irina Bakunina

Biomedicines 2021, 9(5), 510; https://doi.org/10.3390/biomedicines9050510 - 5 May 2021

Cited by 4 | Viewed by 2720

Abstract

During a search for glycosidase inhibitors among marine natural products, we applied an integrated in vitro and in silico approach to evaluate the potency of some aaptamines and makaluvamines isolated from marine sponges on the hydrolyzing activity of α-N-acetylgalactosaminidase (α-NaGalase) from human cancer cells and the recombinant α-D-galactosidase (α-PsGal) from a marine bacterium Pseudoalteromonas sp. KMM 701. These alkaloids showed no direct inhibitory effect on the cancer α-NaGalase; but isoaaptamine (2), 9-demethylaaptamine (3), damirone B (6), and makaluvamine H (7) reduced the expression of the enzyme in the human colorectal adenocarcinoma cell line DLD-1 at 5 μM. Isoaaptamine (2), 9-demethylaaptamine (3), makaluvamine G (6), and zyzzyanone A (7) are slow-binding irreversible inhibitors of the bacterial α-PsGal with the inactivation rate constants (k_inact) 0.12 min⁻¹, 0.092 min⁻¹, 0.079 min⁻¹, and 0.037 min⁻¹, as well as equilibrium inhibition constants (K_i) 2.70 µM, 300 µM, 411 µM, and 105 µM, respectively. Docking analysis revealed that these alkaloids bind in a pocket close to the catalytic amino acid residues Asp451 and Asp516 and form complexes, due to π-π interactions with the Trp308 residue and hydrogen bonds with the Lys449 residue. None of the studied alkaloids formed complexes with the active site of the human α-NaGalase. Full article

(This article belongs to the Special Issue Biomedicine from the Sea)

► Show Figures

Figure 1

14 pages, 1692 KiB

Open AccessArticle

The Effect of Fucoidan from the Brown Alga Fucus evanescence on the Activity of α-N-Acetylgalactosaminidase of Human Colon Carcinoma Cells

by Irina Bakunina, Oksana Chadova, Olesya Malyarenko and Svetlana Ermakova

Mar. Drugs 2018, 16(5), 155; https://doi.org/10.3390/md16050155 - 10 May 2018

Cited by 9 | Viewed by 7353

Abstract

α-N-acetylgalactosaminidase (EC 3.2.1.49) (alpha-NaGalase) catalyzes the hydrolysis of N-acetamido-2-deoxy-α-d-galactoside residues from non-reducing ends of various complex carbohydrates and glycoconjugates. It is known that human cancer cells express an alpha-NaGalase, which accumulates in the blood plasma of patients. The enzyme deglycosylates the Gc protein-derived macrophage activating factor (GcMAF) and inhibits macrophage activity acting as an immunosuppressor. The high specific activity 0.033 ± 0.002 μmol mg⁻¹ min⁻¹ of the enzyme was found in human colon carcinoma cells DLD-1. The alpha-NaGalase of DLD-1 cells was isolated and biochemical characterized. The enzyme exhibits maximum activity at pH 5.2 and temperature 55 °C. The K_m is 2.15 mM, V_max–0.021 μmol min⁻¹ mL⁻¹, k_cat–1.55 min⁻¹ and k_cat/K_m–0.72 min⁻¹ mM⁻¹ at 37 °C, pH 5.2. The effects of fucoidan from the brown alga Fucus evanescence on the activity of alpha-NaGalase in human colon carcinoma DLD-1 cells and on the biosynthesis of this enzyme were investigated. It was shown that fucoidan did not inhibit free alpha-NaGalase, however, it reduced the expression of the enzyme in the DLD-1 cells at IC₅₀ 73 ± 4 μg mL⁻¹. Full article

(This article belongs to the Special Issue Seaweeds and Their Biological Actions)

► Show Figures

Figure 1

Search Results (3)

Further Information

Guidelines

MDPI Initiatives

Follow MDPI

Saved Queries

Search Filter Reset All

Years

Feature Papers

Subjects

Journals

Article Types

Countries / Regions

Search Results (3)

Further Information

Guidelines

MDPI Initiatives

Follow MDPI