FIP-sch2, a new fungal immunomodulatory protein from Stachybotrys chlorohalonata, suppresses proliferation and migration in lung cancer cells

Appl Microbiol Biotechnol. 2017 Apr;101(8):3227-3235. doi: 10.1007/s00253-016-8030-6. Epub 2017 Jan 12.

Abstract

Fungal immunomodulatory protein (FIP)-sch2, an immunomodulatory protein identified in the ascomycete Stachybotrys chlorohalonata by a sequence similarity search, is a novel member of the FIP family. FIP-sch2 shares high sequence identity, structure, and evolutionary conservation with previously reported FIPs. It was satisfactorily expressed in Escherichia coli with a glutathione S-transferase (GST) tag and purified by GST-affinity magnetic beads. To characterize the direct antitumor effects, human lung adenocarcinoma A549 cells were treated with different concentrations of recombinant FIP (rFIP)-sch2 in vitro, and the results showed that rFIP-sch2 could reduce cell viability dose-dependently with a half-maximal inhibitory concentration (IC50) of 9.48 μg/mL. Furthermore, rFIP-sch2 at 8 μg/mL could significantly induce apoptosis and interrupt migration in A549 cells. Notably, the antitumor effect of rFIP-sch2 was equivalent to that of rLZ-8 but was obviously increased compared to rFIP-fve. In addition, the exploration of the antitumor mechanism suggested that rFIP-sch2 induced lung cancer cell death by activating apoptosis and inhibiting migration. Our results indicated that rFIP-sch2 was a promising candidate for use in future cancer therapy.

Keywords: Apoptosis; Fungal immunomodulatory protein; Migration; Proliferation.

MeSH terms

  • A549 Cells
  • Apoptosis / drug effects
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Escherichia coli / genetics
  • Fungal Proteins / genetics
  • Fungal Proteins / isolation & purification
  • Fungal Proteins / pharmacology*
  • Glutathione Transferase / genetics
  • Humans
  • Immunomodulation*
  • Lung Neoplasms / pathology*
  • Real-Time Polymerase Chain Reaction
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / pharmacology
  • Sequence Alignment
  • Stachybotrys / chemistry*
  • Stachybotrys / genetics
  • Stachybotrys / isolation & purification

Substances

  • Fungal Proteins
  • Recombinant Proteins
  • Glutathione Transferase