Antitumor activity of Tigerinin-1: Necroptosis mediates toxicity in A549 cells

Abstract

Background: Tigerinins are antimicrobial peptides (AMPs) derived from the skin secretions of the Indian bullfrog Hoplobatrachus tigerinus.

Methods: Tigerinin-1 (FCTMIPIPRCY-Am) peptide was synthesized by solid-phase Fmoc chemistry and investigated its antitumor activities.

Results: Tigerinin-1 was cytotoxic to human cancer cells. It causes necrosis by damaging the cell membrane and loss of lysosome integrity. Tigerinin-1triggers the expression of necroptosis pathway proteins. It generates reactive oxygen species (ROS) and induces oxidative stress-mediated genotoxicity. Tigerinin-1 inhibits cancer cell proliferation, reduces neovascularization, and down-regulates the vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR2), and fibroblast growth factor (FGF) genes.

Conclusions: Tigerinin-1 exhibited its potent antitumor properties in this study.

General significance: Tigerinin-1 can be beneficial for developing novel therapeutics for cancer.

Keywords: Anti-angiogenesis; Anticancer peptides; Cytotoxicity; Human cancer cell lines; Necroptosis; Tigerinin-1.