Abstract
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 GSK3β 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 LiCl. Zeb’s suppressive effects were associated with activation of the cAMP/PKA/CREB pathway, differing from mechanisms of 17-AAG and LiCl.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReference
Suzuki M, Shinohara F, Nishimura K et al (2007) Epigenetic regulation of chemosensitivity to 5-fluorouracil and cisplatin by zebularine in oral squamous cell carcinoma. Int J Oncol 31:1449–1456
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer
About this paper
Cite this paper
Suzuki, M., Shinohara, F., Endo, M., Sugazaki, M., Echigo, S., Rikiishi, H. (2010). Effects of zebularine on the apoptosis of 5-fluorouracil via cAMP/PKA/CREB pathway in HSC-3 cells. In: Sasano, T., Suzuki, O. (eds) Interface Oral Health Science 2009. Springer, Tokyo. https://doi.org/10.1007/978-4-431-99644-6_15
Download citation
DOI: https://doi.org/10.1007/978-4-431-99644-6_15
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-99643-9
Online ISBN: 978-4-431-99644-6
eBook Packages: MedicineMedicine (R0)