Flammutoxin, a Degradation Product of Transepithelial Electrical Resistance-Decreasing Protein, Induces Reactive Oxygen Species and Apoptosis in HepG2 Cells
Author:
Wu Jianguo1ORCID, Nong Yu1, Chen Bingzhi2ORCID, Jiang Yuji2, Chen Yuanhao1, Wei Chuanzheng1, Tao Yongxin13, Xie Baogui1
Affiliation:
1. Mycological Research Center, College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China 2. College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China 3. College of Horticulture, Fujian Agriculture and Forestry University, Fuzhou 350002, China
Abstract
Proteins from Flammulina filiformis were prepared by sodium chloride extraction and fractionated by ammonium sulfate precipitation with increasing saturation degrees to obtain the protein fractions Ffsp-30, Ffsp-50, Ffsp-70, Ffsp-90, and Ffp-90. Among these protein fractions, Ffsp-50 possessed the most significant cytotoxic effect against three human gastrointestinal cancer cell lines, viz. HT-29, SGC-7901, and HepG2. SDS-PAGE and MALDI-TOF/TOF MS/MS analyses revealed that flammutoxin (FTX) was present as a dominating protein in Ffsp-50, which was further evidenced by HPLC-MS/MS determination. Furthermore, native FTX was purified from Ffsp-50 with a molecular weight of 26.78 kDa, exhibiting notable cytotoxicity against gastrointestinal cancer cell lines. Both Ffsp-50 and FTX exposure could enhance intercellular reactive oxygen species (ROS) generation and induce significant apoptosis in HepG2 cells. FTX was identified to be relatively conserved in basidiomycetes according to phylogenetic analysis, and its expression was highly upregulated in the primordium as well as the pileus of the fruiting body from the elongation and maturation stages, as compared with that in mycelium. Taken together, FTX could remarkably inhibit cell growth and induce ROS and apoptosis in HepG2 cells, potentially participating in the growth and development of the fruiting body. These findings from our investigation provided insight into the antigastrointestinal cancer activity of FTX, which could serve as a biological source of health-promoting and biomedical applications.
Funder
Natural Science Foundation for Distinguished Young Scholars of Fujian Agriculture and Forestry University of China National Key R&D Program of China Seed Industry Innovation and Industrialization Project of Fujian Province of China
Subject
Plant Science,Health Professions (miscellaneous),Health (social science),Microbiology,Food Science
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