PFR peptide, one of the antimicrobial peptides identified from the derivatives of lactoferrin, induces necrosis in leukemia cells.
PFR peptide, one of the antimicrobial peptides identified from the derivatives of lactoferrin, induces necrosis in leukemia cells.
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PFR肽是从乳铁蛋白的衍生物中鉴定出的抗菌肽之一，可诱导白血病细胞坏死。
DOI：
10.1038/srep20823
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发表时间：
2016-02-10
影响因子：
4.6
通讯作者：
Fu CY
中科院分区：
文献类型：
--
作者：
Lu Y;Zhang TF;Shi Y;Zhou HW;Chen Q;Wei BY;Wang X;Yang TX;Chinn YE;Kang J;Fu CY
LF 11 -322（PFWRIRR-NH 2）（PFR肽）是一种来源于人乳铁蛋白的9个氨基酸残基的肽片段，具有强效的抗细菌细胞毒性。我们在这里报告的发现和表征其在白血病细胞中的抗肿瘤活性。PFR肽通过诱导细胞死亡抑制MEL和HL-60白血病细胞的增殖，而不存在经典的凋亡特征，包括染色质浓缩、Annexin V染色、Caspase活化和促凋亡蛋白丰度增加。相反，在PFR肽处理后观察到坏死细胞死亡，如通过增加细胞内PI染色和LDH释放、诱导膜破坏和上调细胞内钙水平所证明的。除坏死性细胞死亡外，PFR肽还诱导G 0/G1期细胞阻滞。此外，PFR肽在体内表现出良好的抗肿瘤活性和耐受性。这些发现为抗菌肽作为一种潜在的白血病治疗药物提供了新的线索。
LF11-322 (PFWRIRIRR-NH2) (PFR peptide), a nine amino acid-residue peptide fragment derived from human lactoferricin, possesses potent cytotoxicity against bacteria. We report here the discovery and characterization of its antitumor activity in leukemia cells. PFR peptide inhibited the proliferation of MEL and HL-60 leukemia cells by inducing cell death in the absence of the classical features of apoptosis, including chromatin condensation, Annexin V staining, Caspase activation and increase of abundance of pro-apoptotic proteins. Instead, necrotic cell death as evidenced by increasing intracellular PI staining and LDH release, inducing membrane disruption and up-regulating intracellular calcium level, was observed following PFR peptide treatment. In addition to necrotic cell death, PFR peptide also induced G0/G1 cell cycle arrest. Moreover, PFR peptide exhibited favorable antitumor activity and tolerability in vivo. These findings thus provide a new clue of antimicrobial peptides as a potential novel therapy for leukemia.