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

• Published in: Biochimica et biophysica acta. General subjects Vol. 1866; no. 9; p. 130182
• Main Authors: Antony, Anet, Olakkaran, Shilpa, Purayil, Anupama Kizhakke, Shekh, Shamasoddin, Gowd, Konkallu Hanumae, Gurushankara, Hunasanahally Puttaswamygowda
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2022
• Subjects: angiogenesis; Anti-angiogenesis; Anticancer peptides; antimicrobial peptides; antineoplastic activity; cell membranes; cell proliferation; chemistry; Cytotoxicity; fibroblast growth factors; genotoxicity; Hoplobatrachus tigerinus; Human cancer cell lines; humans; lysosomes; Necroptosis; necrosis; neoplasm cells; reactive oxygen species; therapeutics; Tigerinin-1; vascular endothelial growth factor receptor-2; vascular endothelial growth factors; Tigerinin-1; Cytotoxicity; Anticancer peptides; Anti-angiogenesis; Necroptosis; Human cancer cell lines
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2022.130182

Tigerinins are antimicrobial peptides (AMPs) derived from the skin secretions of the Indian bullfrog Hoplobatrachus tigerinus. Tigerinin-1 (FCTMIPIPRCY-Am) peptide was synthesized by solid-phase Fmoc chemistry and investigated its antitumor activities. 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. Tigerinin-1 exhibited its potent antitumor properties in this study. Tigerinin-1 can be beneficial for developing novel therapeutics for cancer. [Display omitted] •Tigerinin-1 peptide synthesized by solid-phase Fmoc chemistry.•Tigerinin-1 is cytotoxic to human cancer cells.•Tigerinin-1 triggers the expression of necroptosis proteins.•Tigerinin-1-induced necroptosis leads to oxidative stress-mediated genotoxicity.•Tigerinin-1 has anti-angiogenic nature.