虎杖苷-1 的抗肿瘤活性：坏死性凋亡介导 A549 细胞毒性。

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

机构信息

Department of Zoology, School of Biological Sciences, Central University of Kerala, Tejaswini Hills, Periya 671 320, Kasaragod, India.

Department of Chemistry, School of Chemical Sciences, Central University of Karnataka, Kalaburagi 585 367, Karnataka, India.

出版信息

Biochim Biophys Acta Gen Subj. 2022 Sep;1866(9):130182. doi: 10.1016/j.bbagen.2022.130182. Epub 2022 May 28.

DOI:10.1016/j.bbagen.2022.130182

PMID:35636711

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.

摘要

背景

虎纹蛙抗菌肽（AMPs）来源于印度牛蛙的皮肤分泌物。

方法

通过固相 Fmoc 化学合成虎纹蛙抗菌肽-1（FCTMIPIPRCY-Am）肽，并研究其抗肿瘤活性。

结果

虎纹蛙抗菌肽-1对人癌细胞具有细胞毒性。它通过破坏细胞膜和溶酶体完整性导致坏死。虎纹蛙抗菌肽-1 触发坏死性凋亡途径蛋白的表达。它产生活性氧（ROS）并诱导氧化应激介导的遗传毒性。虎纹蛙抗菌肽-1抑制癌细胞增殖，减少新生血管形成，并下调血管内皮生长因子（VEGF）、血管内皮生长因子受体 2（VEGFR2）和成纤维细胞生长因子（FGF）基因。