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Cited by 0Fungal Biology and ApplicationsAntimicrobial Peptides and ActivitiesMicrobial Natural Products and Biosynthesis

The DOI matches its Crossref record; 21 of the 21 references it cites were found in a registry or an index.

Characterization and anticancer bioactivity of the fungal immunomodulatory protein FIP-Gre from Ganoderma resinaceum

Open access
Ameen, Rubab, Sumrin, Aleena·2026·Molecular Biology Reports
DOI 10.1007/s11033-026-11649-6

Published version of a preprint

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Abstract

Background Natural products remain rich sources of anticancer agents. Fungal immunomodulatory proteins (FIPs) from medicinal mushrooms show direct in vitro tumor inhibition; we investigated a new FIP, FIP-Gre, from Ganoderma resinaceum. Methods FIP-Gre was identified by genome mining (LZ8 query), modeled by AlphaFold2, and assessed by docking/100-ns MD (EGFR, c-Met). Recombinant FIP-Gre was produced in E. coli BL21 (DE3)/pET-29a (+), purified by Ni-NTA (~ 12.5 kDa), and tested for hemagglutination, antibacterial activity, cytotoxicity (A549, HepG2, MCF-7; HEK-293 control), and apoptosis markers in A549 cells (8 µg/mL). Results FIP-Gre shares 90% identity with LZ8, contains a conserved Fve-type domain, and adopts a stable β-strand-rich fold. Docking/MD suggest strong, stable binding to EGFR and c-Met. FIP-Gre agglutinated mouse RBCs at 4 µg/mL, showed no antibacterial activity, and selectively inhibited cancer cells with IC₅₀ values of 21.27 µg/mL (A549), 29.96 µg/mL (HepG2), and 43.34 µg/mL (MCF-7) while showing no toxicity toward normal HEK-293 cells. At 8 µg/mL, FIP-Gre significantly induced apoptosis in A549 cells by upregulating Bax, Caspase-3, Caspase-9, and p53, and downregulating Bcl-2, indicating activation of the mitochondrial apoptotic pathway. Conclusion FIP-Gre is a structurally robust, mushroom-derived protein with selective in vitro anticancer activity and predicted RTK engagement, supporting its development, particularly against lung carcinoma.

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Cites

Research works printed but not linked: 11

  1. Li S, Gong Y, Yao Y et al (2017) FIP-sch2, a new fungal immunomodulatory protein from Stachybotrys chlorohalonata, suppresses proliferation and migration in lung cancer cells. Appl Microbiol Biotechnol 101:3227–3235. https://doi.org/10.1007/s00253-017-8101-4 · DOI
  2. Ejike UC, Gong Y, Li S et al (2020) New advances and potentials of fungal immunomodulatory proteins for therapeutic purposes. Crit Rev Biotechnol 40(8):1172–1190. https://doi.org/10.1080/07388551.2020.1822294 · DOI
  3. Patel SA, Nilsson MB, Le X et al (2023) Molecular mechanisms and future implications of VEGF/VEGFR in cancer therapy. Clin Cancer Res 29(1):30–39. https://doi.org/10.1158/1078-0432.CCR-22-2045 · DOI
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  6. Wang Y, Chen G, Li Y et al (2019) Identification of a novel anti-cancer protein, FIP-bbo, from Botryobasidium botryosum and protein structure analysis using molecular dynamic simulation. Sci Rep 9:42104. https://doi.org/10.1038/s41598-019-42104-6 · DOI
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  9. Qu ZW, Sun X, Li S et al (2018) Recombinant expression and bioactivity comparison of four typical fungal immunomodulatory proteins from three main Ganoderma species. BMC Biotechnol 18:48. https://doi.org/10.1186/s12896-018-0488-6 · DOI
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  11. Yeh CM, Yeh CK, Chen PC et al (2008) Extracellular expression of a functional recombinant Ganoderma lucidum immunomodulatory protein by Bacillus subtilis and Lactococcus lactis. Appl Environ Microbiol 74(4):1039–1049. https://doi.org/10.1128/AEM.02243-07 · DOI

Metadata

Authors
Ameen, R., & Sumrin, A.
Affiliations
University of the Punjab (PK)
Corresponding author
  • Ameen, Rubab
  • Sumrin, Aleena
ORCID
Sumrin, Aleena
Venue
Molecular Biology Reports
Publisher
Springer Science and Business Media LLC
Published
2026-03-12
Volume
53
Issue
1
ISSN
  • 0301-4851 (ISSN-L)
  • 1573-4978
DOI
10.1007/s11033-026-11649-6
OpenAlex
W7135084450
Cited by
0
References
21
FWCI
0.00
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Biology Reports (publishedVersion)
  • Research Square (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
University of the Punjab
Topics
  • Health Sciences › Medicine › Pharmacology (medical) › Fungal Biology and Applications
  • Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
  • Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Microbial Natural Products and Biosynthesis
Keywords
fungal immunomodulatory protein, Ganoderma resinaceum, medicinal mushrooms, anticancer activity, EGFR, c-Met, receptor tyrosine kinase, apoptosis, mitochondrial apoptosis, lung cancer, hemagglutination, cytotoxicity, protein structure prediction, protein-protein docking
MeSH terms
A549 Cells, Animals, Antineoplastic Agents, Fungal Proteins, Humans, Immunologic Factors, Recombinant Proteins, Apoptosis, Proto-Oncogene Proteins c-met, Ganoderma, Cell Line, Tumor, Mice, Hep G2 Cells, HEK293 Cells, MCF-7 Cells, Molecular Docking Simulation, ErbB Receptors

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