The cytotoxic effects of human neutrophil peptide-1 (HNP1) and lactoferrin on oral squamous cell carcinoma (OSCC) in vitro.
Alpha-defensin or human neutrophil peptide-1 (HNP1) is a neutrophil-derived antimicrobial peptide with cytotoxic effects towards cancer cells. Lactoferrin is also stored in human neutrophils and is a glycoprotein involved in mediating cytotoxicity towards tumour cells. This study investigated the sensitivity of normal oral keratinocyte and oral squamous cell carcinoma (OSCC) cells to HNP1 and lactoferrin in various combinations. A concentration of 100 microg/ml HNP1 induced the most significant cytotoxic effect on both normal and OSCC cells. Lactoferrin (12.5, 25 and 250 microg/ml) also significantly induced cell death in OSCC cells after 72 h. Of note, a combination of 10 microg/ml HNP1 and 50 microg/ml lactoferrin induced a differential effect, not observed with either concentration alone, which stimulated proliferation in normal cells, but induced cell death in OSCC cells throughout the study. These results indicate a potentially important co-operative role for HNP1 and lactoferrin in facilitating a selective cytotoxic effect on tumour cells.
Oral Science Research Centre, School of Medicine and Dentistry, Queen's University Belfast, Royal Victoria Hospital, Grosvenor Road, Belfast BT12 6BP, Northern Ireland, United Kingdom.
Scott T W
ST
McKeown
Fionnuala T
FT
Lundy
John
J
Nelson
Derek
D
Lockhart
Chris R
CR
Irwin
C Gerard
CG
Cowan
John J
JJ
Marley
D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology; D007781:Lactoferrin / Q000494:pharmacology*; D009061:Mouth Mucosa / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D009062:Mouth Neoplasms / Q000201:enzymology / Q000473:pathology*; D014407:Tumor Cells, Cultured; D023084:alpha-Defensins / Q000494:pharmacology*
D023084:alpha-Defensins; C406413:human neutrophil peptide 1; D007781:Lactoferrin