Effects of zebularine on the apoptosis of 5-fluorouracil via cAMP/PKA/CREB pathway in HSC-3 cells

被引：0
|
作者：
Suzuki, Maiko [1 ]
Shinohara, Fumiaki [2 ]
Endo, Manabu [2 ]
Sugazaki, Masaki [2 ]
Echigo, Seishi [2 ]
Rikiishi, Hidemi [1 ]
机构：
[1] Tohoku Univ, Grad Sch Dent, Dept Microbiol & Immunol, Aoba Ku, 4-1 Seiryo Machi, Sendai, Miyagi 9808575, Japan
[2] Tohoku Univ, Grad Sch Dent, Dept Oral Surgery, Aoba Ku, Sendai, Miyagi 9808575, Japan
来源：
INTERFACE ORAL HEALTH SCIENCE 2009 | 2010年
关键词：
zebularine; methylation; 5-fluorouracil; apoptosis; OSCC;
D O I：
10.1007/978-4-431-99644-6_15
中图分类号：
R78 [口腔科学];
学科分类号：
1003 ;
摘要：
During tumorigenesis, tumor suppressor and tumor-related genes are commonly silenced by aberrant DNA methylation in their promoter regions, which is one of the important determinants of susceptibility to 5-fluorouracil (5-FU) in oral squamous cell carcinoma cells. We investigated the effect of a DNA methyltransferase (DNMT) inhibitor, zebularine (Zeb), on the chemosensitivity of 5-FU and cisplatin (CDDP), and compared the molecular mechanism of action with those of a GSK3 beta inhibitor, LiCl, and an Hsp90 inhibitor, 17-AAG. A significant apoptotic effect by a combination of Zeb or 17-AAG was found in CDDP treatment; however, considerable suppression of 5-FU-induced apoptosis was observed after incubation with Zeb, 17-AAG, or LiCI. Zeb's suppressive effects were associated with activation of the cAMP/PKA/CREB pathway, differing from mechanisms of 17-AAG and LiCl.
引用
收藏
页码：111 / +
页数：2
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