A fish antimicrobial peptide, tilapia hepcidin TH2-3, shows potent antitumor activity against human fibrosarcoma cells.
As part of a continuing search for potential anticancer drug candidates from antimicrobial peptides of marine organisms, tilapia (Oreochromis mossambicus) hepcidin TH2-3 was evaluated in several tumor cell lines. The results indicated that TH2-3, a synthetic 20-mer antimicrobial peptide, specifically inhibited human fibrosarcoma cell (HT1080 cell line) proliferation and migration. The way in which TH2-3 inhibited HT1080 cell growth was then studied. TH2-3 inhibited HT1080 cell growth in a concentration-dependent manner according to an MTT analysis, which was confirmed by a soft-agar assay and AO/EtBr staining. Scanning electron microscopy revealed that TH2-3 caused lethal membrane disruption in HT1080 cancer cells, and a wound healing assay supported that TH2-3 decreased the migration of HT1080 cells. In addition, c-Jun mRNA expression was downregulated after treatment with TH2-3 for 48-96 h compared to the untreated group. These findings suggest a mechanism of cytotoxic action of TH2-3 and indicate that TH2-3 may be a promising chemotherapeutic agent against human fibrosarcoma cells.
Chen
Jyh-Yih
JY
Marine Research Station, Institute of Cellular and Organismic Biology, Academia Sinica, 23-10 Dahuen Rd., Jiaushi, Ilan 262, Taiwan. zoocjy@gate.sinica.edu.tw
Lin
Wei-Ju
WJ
Lin
Tai-Lang
TL
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D019556:COS Cells; D002154:Calpain / Q000235:genetics; D053148:Caspase 3 / Q000235:genetics; D056649:Cathepsin G; D002403:Cathepsins / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000378:metabolism; D029941:Fish Proteins / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006367:HeLa Cells; D064451:Hepcidins; D006801:Humans; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics; D017210:Tilapia; D014945:Wound Healing / Q000187:drug effects
D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; D029941:Fish Proteins; C578702:HAMP protein, human; D064451:Hepcidins; D016755:Proto-Oncogene Proteins c-jun; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D002154:Calpain; C494426:Capn5 protein, human; D053148:Caspase 3