Production of L-asparaginase from Candida utilis by solid-state fermentation: a comprehensive assessment of its antiproliferative potential on glioblastoma cells
World Journal of Microbiology and Biotechnology, vol.41, no.12, 2025 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 41 Issue: 12
- Publication Date: 2025
- Doi Number: 10.1007/s11274-025-04638-7
- Journal Name: World Journal of Microbiology and Biotechnology
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, ABI/INFORM, BIOSIS, Compendex, Environment Index, MEDLINE
- Keywords: Antiproliferative, Candida utilis, Glioblastoma, L-asparaginase, Solid state fermentation
- Kütahya Health Sciences University Affiliated: Yes
Abstract
L-asparaginase (L-ASNase) is an enzyme that depletes asparagine, a key amino acid for cancer cell survival, producing aspartic acid and ammonia. Beyond its food industry applications, L-ASNase is a clinically important agent against acute lymphoblastic leukemia (ALL). In this study, L-ASNase was produced and purified from Candida utilis via solid-state fermentation. Optimization on wheat bran identified 2 mL inoculation volume, 60% moisture, and a 4-day fermentation period as the optimal conditions, yielding 172.5 U/mL activity. The purified enzyme was tested against glioblastoma (GBM) cell lines, showing IC₅₀ values of 0.4 U/mL for U87MG and 1.8 U/mL for T98G, with minimal toxicity toward normal HaCaT cells. Apoptotic effects were confirmed by DAPI/F-actin and Giemsa staining, while wound healing and clonogenic assays revealed inhibition of cell migration and colony formation. RT-qPCR analysis demonstrated downregulation of the Survivin gene, a key survival regulator. These findings highlight L-ASNase’s potent antiproliferative, anti-migratory, and pro-apoptotic effects, underscoring its potential as an adjuvant therapy for GBM.