2. Academic Validation
  3. New fungal protein from Pleurotus ferulae lanzi induces AMPK-mediated autophagy and G1-phase cell cycle arrest in A549 lung cancer cells

New fungal protein from Pleurotus ferulae lanzi induces AMPK-mediated autophagy and G1-phase cell cycle arrest in A549 lung cancer cells

  • Int J Biol Macromol. 2023 Jun 16;244:125453. doi: 10.1016/j.ijbiomac.2023.125453.
Meng-Han Liu 1,  Fang Liu 2,  Tzi Bun Ng 3,  Zhao-Kun Liu 4
Affiliations

Affiliations

  • 1 Department of Microbiology, The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China.
  • 2 Department of Microbiology, The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China. Electronic address: [email protected].
  • 3 School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China. Electronic address: [email protected].
  • 4 Research Institute of Public Health, School of Medicine, Nankai University, Tianjin 300071, China. Electronic address: [email protected].
PMID: 37330099 DOI: 10.1016/j.ijbiomac.2023.125453
Abstract

A new protein, designated PFAP, with activity against non-small cell lung Cancer (NSCLC), was isolated from Pleurotus ferulae lanzi, a medicinal and edible mushroom. The purification method involved hydrophobic interaction chromatography on a HiTrap Octyl FF column and gel filtration on a Superdex 75 column. Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) revealed a single band with a molecular weight of 14.68 kDa. Following de novo sequencing and liquid chromatography-tandem mass spectrometry, PFAP was identified as a protein consisting of 135 amino acid residues, with a theoretical molecular weight of 14.81 kDa. Tandem mass tag (TMT)™-based quantitative proteomic analysis and western blotting revealed that AMP-activated protein kinase (AMPK) was significantly upregulated in NSCLC A549 cells, following PFAP treatment. The downstream regulatory factor mammalian target of rapamycin (mTOR) was suppressed, resulting in the activation of Autophagy and upregulated expressions of P62, LC3 II/I, and other related proteins. PFAP blocked NSCLC A549 cells in the G1 phase of the cell cycle via upregulating P53 and P21, while subsequently downregulating the expression of cyclin-dependent kinases. PFAP suppresses tumour growth via the same mechanism in a xenograft mouse model in vivo. These results demonstrate that PFAP is a multifunctional protein with anti-NSCLC properties.

Keywords

AMPK/mTOR pathway; Anti-NSCLC; PFAP; Pleurotus ferulae lanzi.

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