C-terminal domain of human CAP18 antimicrobial peptide induces apoptosis in oral squamous cell carcinoma SAS-H1 cells.
Mammalian myeloid and epithelial cells express many antimicrobiotic peptides that contribute to innate host defense against invading microbes. In the present study, a 27-mer peptide of the C-terminal domain (hCAP18(109-135)) and analogs of the antimicrobial peptide human cathelicidin LL-37/human cationic antimicrobial protein 18 (hCAP18) were examined for tumoricidal activity. In vitro results showed that hCAP18(109-135) induced apoptosis in human oral squamous cell carcinoma (OSCC), SAS-H1 cells. The hCAP18(109-135) induced mitochondrial depolarization and apoptosis in SAS-H1 cells, but not in healthy human gingival fibroblasts (HGF) and human keratinocyte line HaCaT cells. Caspases were not activated during hCAP18(109-135)-induced apoptosis in SAS-H1 cells. The results indicate that hCAP18(109-135) may induce caspase-independent apoptosis in OSCC but not in normal cells. hCAP18(109-135) can therefore be a useful anti-tumor therapeutic agent in the treatment of OSCC.
1st Department of Oral and Maxillofacial Surgery, School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu 1757, 061-0293, Japan. kokumura@hoku-iryo-u.ac.jp
Kazuhiko
K
Okumura
Akifumi
A
Itoh
Emiko
E
Isogai
Kimiharu
K
Hirose
Yoichiro
Y
Hosokawa
Yoshihiro
Y
Abiko
Takatoshi
T
Shibata
Michimasa
M
Hirata
Hiroshi
H
Isogai
D000890:Anti-Infective Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D054804:Cathelicidins; D016923:Cell Death; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000473:pathology; D010455:Peptides / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D013997:Time Factors
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D010455:Peptides; D004247:DNA; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases