The fucose‐specific lectin ANL from Aspergillus niger possesses anti‐cancer activity by inducing the intrinsic apoptosis pathway in hepatocellular and colon cancer cells
| Autor: | Shivakumar Belur, Barry J. Campbell, Shashikala R. Inamdar, Narasimhappagari Jagadeesh |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Carcinoma Hepatocellular Clinical Biochemistry Antineoplastic Agents Biochemistry Fucose Fungal Proteins 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Lectins Humans chemistry.chemical_classification biology Liver Neoplasms Intrinsic apoptosis Mucin Lectin Hep G2 Cells Cell Biology General Medicine Molecular biology digestive system diseases 030104 developmental biology chemistry Apoptosis 030220 oncology & carcinogenesis Colonic Neoplasms biology.protein Aspergillus niger Antibody Glycoprotein Alpha-fetoprotein HT29 Cells |
| Zdroj: | CELL BIOCHEMISTRY AND FUNCTION |
| ISSN: | 1099-0844 0263-6484 |
| DOI: | 10.1002/cbf.3605 |
| Popis: | The L-fucose-specific lectin from Aspergillus niger (ANL), isolated from the corneal smears of a keratitis patient was reported earlier. Here, we examined the interaction of ANL with human hepatocellular and colon cancer cells, evaluated its anti-cancer activity and diagnostic potential to detect aberrantly glycosylated tumour-associated serum glycoproteins such as alpha-fetoprotein (AFP). We observed that ANL strongly bound to both HepG2 and HT-29 cell-lines and this interaction was effectively blocked with L-fucose and mucin in a dose and time-dependent manner with an IC50 of 1.25 and 5 μg/mL for HepG2 and HT-29 cells respectively at 48 hours. ANL treatment increased hypodiploidy and decreased the number of HepG2 cell in G0 -G1 phase at both 24 and 48 hours. Furthermore, ANL increased the level of apoptosis in both HepG2 and HT-29 cells in a time-dependent manner via enhanced production of reactive oxygen species and altered mitochondrial membrane potential, indicative of intrinsic apoptotis pathway activation. Immunoblot analysis confirmed the time-dependent elevation of levels of cytochrome c, initiator caspase-9 and activation of caspase-3. ANL immunohistochemistry on colon cancer tissue and quantification of AFP in HCC patient serum samples by developing an ANL-anti-AFP antibody sandwich enzyme-linked immunosorbent assay confirmed the diagnostic potential of ANL. Here, interaction of ANL with AFP could be effectively blocked in the presence of competing fucose-bearing glycans. We found ANL to be more sensitive than Lens culinaris lectin, a well-known fucose-specific lectin and currently used diagnostic agent. ANL can be further explored as a diagnostic and anti-cancer agent. |
| Databáze: | OpenAIRE |
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