title: PFR peptide, one of the antimicrobial peptides identified from the derivatives of lactoferrin, induces necrosis in leukemia cells.
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.
authors: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China.|Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Hangzhou 310018, China.
authors: Yan
authors: Y
authors: Lu
authors: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China.|Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Hangzhou 310018, China.
authors: Teng-Fei
authors: TF
authors: Zhang
authors: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China.|Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Hangzhou 310018, China.
authors: Yue
authors: Y
authors: Shi
authors: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China.|Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Hangzhou 310018, China.
authors: Han-Wei
authors: HW
authors: Zhou
authors: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China.|Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Hangzhou 310018, China.
authors: Qi
authors: Q
authors: Chen
authors: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China.|Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Hangzhou 310018, China.
authors: Bu-Yun
authors: BY
authors: Wei
authors: Department of Oncology, the 117th Hospital of PLA, 14 Lingyin Road, Hangzhou 310013, China.
authors: Xi
authors: X
authors: Wang
authors: Department of Hematology, Zhejiang Province People's Hospital, Hangzhou, Zhejiang, China.
authors: Tian-Xin
authors: TX
authors: Yang
authors: Institute of Health Sciences, Chinese Academic of Sciences, Shanghai 200031, China.
authors: Y Eugene
authors: YE
authors: Chinn
authors: Cancer Signalling Laboratory, Oncogenic Signalling and Growth Control Program, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria 8006, Australia.
authors: Jian
authors: J
authors: Kang
authors: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China.|Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, Hangzhou 310018, China.|Key Laboratory of Cell-Based Drug and Applied Technology Development in Zhejiang Province, Hangzhou, People's Republic of China.
authors: Cai-Yun
authors: CY
authors: Fu
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D018922:HL-60 Cells; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007781:Lactoferrin / Q000737:chemistry*; D007938:Leukemia / Q000473:pathology; D051379:Mice; D009336:Necrosis / Q000139:chemically induced*; D010455:Peptides / Q000494:pharmacology*
chemical_list: D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; D010455:Peptides; D007781:Lactoferrin