The fucose-specific lectin ANL from <i>Aspergillus niger</i> possesses anti-cancer activity by inducing the intrinsic apoptosis pathway in hepatocellular and colon cancer cells

Jagadeesh, Narasimhappagari, Belur, Shivakumar, Campbell, Barry J ORCID: 0000-0002-7407-012X and Inamdar, Shashikala R (2021) The fucose-specific lectin ANL from <i>Aspergillus niger</i> possesses anti-cancer activity by inducing the intrinsic apoptosis pathway in hepatocellular and colon cancer cells. CELL BIOCHEMISTRY AND FUNCTION, 39 (3). pp. 401-412.

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Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	alpha-apoptosis, Aspergillus niger lectin, cell cycle arrest, lectin-ELISA
Depositing User:	Symplectic Admin
Date Deposited:	12 Feb 2021 08:27
Last Modified:	17 Oct 2023 11:16
DOI:	10.1002/cbf.3605
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3115380