1. PFR peptide, one of the antimicrobial peptides identified from the derivatives of lactoferrin, induces necrosis in leukemia cells
- Author
-
Bu-Yun Wei, Yue Shi, Zhou Hanwei, Qi Chen, Lu Yan, Caiyun Fu, Y. Eugene Chinn, Teng-Fei Zhang, Tianxin Yang, Xi Wang, and Jian Kang
- Subjects
0301 basic medicine ,Programmed cell death ,Cell Survival ,Antimicrobial peptides ,Peptide ,Antineoplastic Agents ,Apoptosis ,HL-60 Cells ,Biology ,Hemolysis ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,Necrosis ,0302 clinical medicine ,Annexin ,Lactoferricin ,Cell Line, Tumor ,Animals ,Humans ,Cytotoxicity ,Cell Proliferation ,chemistry.chemical_classification ,Multidisciplinary ,Leukemia ,Cell Cycle ,Molecular biology ,Disease Models, Animal ,Lactoferrin ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,Female ,Peptides ,Intracellular ,Antimicrobial Cationic Peptides - Abstract
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.
- Published
- 2016
- Full Text
- View/download PDF