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Glucose-methanol-based fed-batch fermentation for the production of recombinant human interferon gamma (rhIFN-γ) and evaluation of its antitumor potential.
Glucose-methanol-based fed-batch fermentation for the production of recombinant human interferon gamma (rhIFN-γ) and evaluation of its antitumor potential.
- Source :
-
Biotechnology and applied biochemistry [Biotechnol Appl Biochem] 2020 Nov; Vol. 67 (6), pp. 973-982. Date of Electronic Publication: 2020 Feb 05. - Publication Year :
- 2020
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Abstract
- Squamous cell carcinoma (SCC) is nonmelanoma skin cancer, which is very common in patients having T-cell immunosuppressant drugs. Anticancerous agents such as cytokines showed effective response on SCC. Human interferon-gamma (hIFN-γ), a type II cytokines, are having potent antiproliferative and immunomodulatory effects. In the current study, the fed-batch cultivation of recombinant Pichia pastoris was carried out, and its effect on cell biomass production, recombinant human interferon-gamma (rhIFN-γ) production, and the overflow metabolites was estimated. P. pastoris GS115 strain coexpressed with 6-phosphogluconolactonase (SOL3) and ribulose-phosphate 3-epimerase (RPE1) gene (GS115/rhIFN-γ/SR) resulted in 60 mg L <superscript>-1</superscript> of rhIFN-γ production, which was twofold higher as compared with the production from GS115/rhIFN-γ strain. The antiproliferative potential of rhIFN-γ was examined on the human squamous carcinoma (A431) cell lines. Cells treated with 80 ng mL <superscript>-1</superscript> of rhIFN-γ exhibited 50% growth inhibition by enhancing the production of intracellular reactive oxygen species levels and disrupting membrane integrity. Our findings highlight a state of art process development strategy for the high-level production of rhIFN-γ and its potential application as a therapeutic drug in SCC therapy.<br /> (© 2019 International Union of Biochemistry and Molecular Biology, Inc.)
- Subjects :
- Batch Cell Culture Techniques
Carcinoma, Squamous Cell metabolism
Carcinoma, Squamous Cell pathology
Cell Line, Tumor
Drug Screening Assays, Antitumor
Glucose pharmacology
Humans
Methanol pharmacology
Recombinant Proteins biosynthesis
Recombinant Proteins genetics
Recombinant Proteins pharmacology
Saccharomycetales growth & development
Antineoplastic Agents pharmacology
Carcinoma, Squamous Cell drug therapy
Interferon-gamma biosynthesis
Interferon-gamma genetics
Interferon-gamma pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1470-8744
- Volume :
- 67
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Biotechnology and applied biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 31811672
- Full Text :
- https://doi.org/10.1002/bab.1868