Butyrate inhibits oral cancer cell proliferation and regulates expression of secretory phospholipase A2-X and COX-2.
Although surgical resection is the first choice for oral cancer, the development of new anti-cancer drugs is of great interest. The effect of the histone deacetylation inhibitor, sodium butyrate (NaBu) on oral cancer cell (OCC) HSC-3 and HSC-4 proliferation in vitro was investigated. The synthesis of rate-limiting enzymes such as sPLA2 (-IIA, -V, -X) and COX-2 was examined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, as well as PGE2 by ELISA. NaBu acted in a concentration-dependent manner. Over 3 mM, it inhibited OCC proliferation, due to increased p21 expression and cell cycle arrest in the G2/M-phase. At low concentration (< or = 1 mM), NaBu showed no effects or enhanced cell proliferation. NaBu also regulated COX-2 and sPLA2-X expression, and augmented PGE2 synthesis in OCC. These results indicate that NaBu is a novel candidate agent for the treatment of oral cancer. The treatment efficacy must be investigated in additional experiments considering NaBu concentration and tumor cell heterogeneity.
Miki
Yukako
Y
Department of Oral and Maxillofacial Surgery, Nihon University School of Dentistry, 1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan. mikiy@dent.nihon-u.ac.jp
Mukae
Shotaro
S
Murakami
Makoto
M
Ishikawa
Yukio
Y
Ishii
Toshiharu
T
Ohki
Hidero
H
Matsumoto
Mitsuhiko
M
Komiyama
Kazuo
K
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002087:Butyrates / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000032:analysis / Q000378:metabolism; D054501:Group II Phospholipases A2; D054505:Group V Phospholipases A2; D054509:Group X Phospholipases A2; D006657:Histones / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D009062:Mouth Neoplasms / Q000201:enzymology*; D010741:Phospholipases A / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D054467:Phospholipases A2
D000970:Antineoplastic Agents; D002087:Butyrates; D006657:Histones; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054505:Group V Phospholipases A2; D054509:Group X Phospholipases A2; C516365:PLA2G10 protein, human; C516299:PLA2G5 protein, human; D054467:Phospholipases A2; D015232:Dinoprostone