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5-Aza-2-deoxycytidine Enhances the Sensitivity of 5-Fluorouracil by Demethylation of the Thymidine Phosphorylase Promoter

5-Aza-2-deoxycytidine Enhances the Sensitivity of 5-Fluorouracil by Demethylation of the Thymidine Phosphorylase Promoter

Yukihiko Nishizawa, Ryuji Ikeda, Masatatsu Yamamoto, Kohichi Kawahara, Yoshinari Shinsato, Kentaro Minami, Mina Nitta, Hideyuki Terazono, Shin-Ichi Akiyama, Tatsuhiko Furukawa, Yasuo Takeda

Anticancer Res. 2019 Aug;39(8):4129-4136.

PMID: 31366497

Abstract:

Background/aim:
5-Aza-2-deoxycytidine (5-Aza-CdR) enhances the sensitivity to 5-fluorouracil (5-FU), but the molecular mechanism is not fully understood. The aim of this study was to investigate the molecular mechanism that enhances the sensitivity to 5-FU treated with 5-Aza-CdR via thymidine phosphorylase (TP).
Materials and methods:
The sensitivity to drugs was determined on several cancer cell lines by the MTT assay. Protein and mRNA levels were examined by immunoblot and RT-PCR, respectively. Gene silencing, binding of Sp1 to DNA and methylation of DNA was performed by siRNA, ChIP assay and sodium bisulfate genomic sequencing, respectively.
Results:
Sp1-binding sites in the TP promoter were methylated in epidermoid carcinoma. 5-Aza-CdR demethylated Sp1-binding sites and enhanced sensitivity to 5-FU.
Conclusion:
Demethylation of Sp1-binding sites by 5-Aza-CdR was a key factor enhancing 5-FU sensitivity, which may enable more effective treatments for cancer patients with the combination of 5-Aza-CdR and 5-FU.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP2353335	5-Aza-2′-deoxycytidine		2353-33-5	Price

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