2006 Fiscal Year Final Research Report Summary
Study of antitumor effect and dendritic cells induced by human Cathelicidin hCAP18.
| Project/Area Number |
17592098
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Health Sciences University of Hokkaido |
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Principal Investigator |
OKUMURA Kazuhiko Health Sciences University of HokkaidoSchool of Dentistry, School of Dentistry, Assistant Professor, 歯学部, 講師 (60194510)
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| Co-Investigator(Kenkyū-buntansha) |
ISOGAI Emiko Health Sciences University of Hokkaido, School of Dentistry, Assistant Professor, 歯学部, 講師 (80113570)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Innate immunity / Acquired immunity / Dendritic cells / Antimicrobial peptides / Cathelicidin family / Anitimicrobial effect / Antitumor effect |
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| Research Abstract |
The hCAP18, a solo human cationic antimicrobial protein of cathelicidin family. Our previously results that hCAP 18 induced loss of mitochondrial membrane potential and death in human oral squamous cell carcinoma (OSCC) cells, but not healthy human keratinocytes and gingival fibroblast cells. Here, we demonstrate that whether hCAP18 peptide-induced apoptosis could mediate a caspase-independent manner in OSCC cells. Our finding that hCAP18-induced apoptosis through a mitochondrial pathway of apoptosis controlled by proapoptotic protein Bax. Continuously, Bax induced the release of Endo G from the mitochondria to cytosol and nucleus, respectively. Furthermore, we investigate the effects of hCAP18 on OSCC growth in vivo, we treated nude mice carrying SAS-H1/GFP cells xenograftings with once-daily injections of hCAP18 peptide. Tumor growth was significantly inhibited after 2 days of hCAP18 treatment, compared to scramble peptide-treated controls. OSCC xenografts tumors from mice treated with hCAP18 displayed predominantly reduction. These results suggest that hCAP18 triggered caspase-independent apoptotic pathway, thereby providing antitumor effect of human OSCC. In addition, hCAP18 peptide promotes dendritic cell differentiation, bridging innate and adaptive immune responses.
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