title: Effects of demethylating agent 5-aza-2(')-deoxycytidine and histone deacetylase inhibitor FR901228 on maspin gene expression in oral cancer cell lines.
abstract: Maspin, which belongs to the serine protease inhibitor (serpin) superfamily, has been proposed as a potent tumor suppressor that inhibits cell motility, invasion, angiogenesis, and metastasis. In the present study, we examined the effects of 5-aza-2(')-deoxycytidine (5-aza-dC), a demethylating agent, and FR901228, a histone deacetylase (HDAC) inhibitor, on maspin expression in oral cancer cell lines. The expression levels of maspin mRNA were divided into two groups, which was the maspin low-expressed and high-expressed cell lines in the 12 oral cancer cell lines. The maspin promoter contained only a few methylated CpG sites in the maspin low-expressed cell lines. Moreover, the methylation status was not altered after 5-aza-dC treatment. However, the transcription of the maspin gene was clearly increased following 5-aza-dC treatment in a number of oral cancer cell lines. These results imply that an action of 5-aza-dC is separate from induction of promoter demethylation. Treatment with FR901228 resulted in a time-dependent stimulation of the re-expression of maspin mRNA as early as 4 h after treatment in the maspin downregulated cells. The re-expression of the maspin gene may contribute to the recuperation of biological functions linked to FR901228 such as an inhibitory effect on tumor angiogenesis and cell invasion. These results indicate that maspin and its target genes may be excellent leads for future studies on the potential benefits of FR901228, a HDAC inhibitor, in cancer therapy.
authors.affiliation: Department of Oral and Maxillofacial Radiology, Graduate Schools of Medicine and Dentistry, Okayama University Graduate Schools, 2-5-1, Shikata-cho, Okayama 700-8525, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Murakami
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Asaumi
authors.forename: Yuu
authors.initials: Y
authors.lastname: Maki
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Tsujigiwa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kuroda
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Nagai
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Yanagi
authors.forename: Tetsuyoshi
authors.initials: T
authors.lastname: Inoue
authors.forename: Shoji
authors.initials: S
authors.lastname: Kawasaki
authors.forename: Noriaki
authors.initials: N
authors.lastname: Tanaka
authors.forename: Nagahide
authors.initials: N
authors.lastname: Matsubara
authors.forename: Kanji
authors.initials: K
authors.lastname: Kishi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D000077209:Decitabine; D047630:Depsipeptides; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000235:genetics; D016147:Genes, Tumor Suppressor; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D015843:Serpins / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D047630:Depsipeptides; D010456:Peptides, Cyclic; D011506:Proteins; D012333:RNA, Messenger; C085344:SERPIN-B5; D015843:Serpins; D000077209:Decitabine; C087123:romidepsin; D001374:Azacitidine