Immunomodulatory Protein from Nectria haematococca Induces Apoptosis in Lung Cancer Cells via the P53 Pathway

International Journal of Molecular Sciences

Shuying Li¹  Fengjiao Xin¹  Bei Fan¹  Lijing Zhang¹  Yan Wang¹  Cong Lu¹  Fengzhong Wang¹  Lizhen Hou¹  Jing-Jing Wang¹ 

[1] Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, No. 2 Yuan Ming Yuan West Road, Beijing 100193, China;

关键词: fungal immunomodulatory protein;    nectria haematococca;    a549;    nmr metabolomics;   

DOI  :  10.3390/ijms20215348

来源: DOAJ

【 摘 要 】

Our previous research has shown that a fungal immunomodulatory protein from Nectria haematococca (FIP-nha) possesses a wide spectrum of anti-tumor activities, and FIP-nha induced A549 apoptosis by negatively regulating the PI3K/Akt signaling pathway based on comparative quantitative proteomics. This study further confirmed that the anti-lung cancer activity of FIP-nha was significantly stronger than that of the reported LZ-8 and FIP-fve. Subsequently, ¹H NMR-based metabolomics was applied to comprehensively investigate the underlying mechanism, and a clear separation of FIP-nha-treated and untreated groups was achieved using pattern recognition analysis. Four potential pathways associated with the anti-tumor effect of FIP-nha on A549 cells were identified, and these were mainly involved in glycolysis, taurine and hypotaurine metabolism, fructose and mannose metabolism, and glycerolipid metabolism. Metabolic pathway analysis demonstrated that FIP-nha could induce A549 cell apoptosis partly by regulating the p53 inhibition pathway, which then disrupted the Warburg effect, as well as through other metabolic pathways. Using RT-PCR analysis, FIP-nha-induced apoptosis was confirmed to occur through upregulation of p53 expression. This work highlights the possible use of FIP-nha as a therapeutic adjuvant for lung cancer treatment.

【 授权许可】

Unknown