Anticancer molecular mechanism of 3'-ethynylcytidine (ECyd).

Y. Wataya, M. Futagami, T. Naito, Y. Uchikubo, T. Yokogawa, K. Takenaka, Hye-Sook Kim, A. Matsuda, M. Fukushima, Y. Kitade

Research output: Chapter in Book/Report/Conference proceedingChapter

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Abstract

The antitumor ribonucleoside analogue 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd), synthesized in 1995, has strong antitumor activity. In mouse mammary tumor FM3A cells, ECyd was rapidly phosphorylated to ECyd-triphosphate (ECTP) as the final product, strongly inhibiting RNA synthesis. The ultimate metabolite of ECyd, ECTP, is stable in cultured FM3A cells with a half-life of 21 hr; ECyd is on a "closed" metabolic pathway to ECTP. Deaminated ECyd derivatives were minor metabolites in the cells treated with Ecyd; therefore cytidine forms probably were not converted to uridine forms at the nucleoside or nucleotide stage. The characteristics of ECyd may be important for the antitumor activity. RNA polymerase in the nucleus was inhibited competitively by ECTP; the ki value was 21 nM. ECyd induced DNA and 28S ribosomal RNA fragnetations. The cleavage pattern of rRNA resembled in that mediated by RNase L. The results suggested that RNase L related mechanisms might be involved in the antitumor activity of ECyd.

Original languageEnglish
Title of host publicationNucleic acids research. Supplement (2001)
Pages233-234
Number of pages2
Edition1
Publication statusPublished - 2001

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28S Ribosomal RNA
Ribonucleosides
Cytidine
Uridine
DNA-Directed RNA Polymerases
Metabolic Networks and Pathways
Nucleosides
Half-Life
Cultured Cells
Nucleotides
RNA
Breast Neoplasms
1-(3-C-ethynylribopentofuranosyl)cytosine
triphosphoric acid
DNA
2-5A-dependent ribonuclease

Cite this

Wataya, Y., Futagami, M., Naito, T., Uchikubo, Y., Yokogawa, T., Takenaka, K., ... Kitade, Y. (2001). Anticancer molecular mechanism of 3'-ethynylcytidine (ECyd). In Nucleic acids research. Supplement (2001) (1 ed., pp. 233-234)

Anticancer molecular mechanism of 3'-ethynylcytidine (ECyd). / Wataya, Y.; Futagami, M.; Naito, T.; Uchikubo, Y.; Yokogawa, T.; Takenaka, K.; Kim, Hye-Sook; Matsuda, A.; Fukushima, M.; Kitade, Y.

Nucleic acids research. Supplement (2001). 1. ed. 2001. p. 233-234.

Research output: Chapter in Book/Report/Conference proceedingChapter

Wataya, Y, Futagami, M, Naito, T, Uchikubo, Y, Yokogawa, T, Takenaka, K, Kim, H-S, Matsuda, A, Fukushima, M & Kitade, Y 2001, Anticancer molecular mechanism of 3'-ethynylcytidine (ECyd). in Nucleic acids research. Supplement (2001). 1 edn, pp. 233-234.
Wataya Y, Futagami M, Naito T, Uchikubo Y, Yokogawa T, Takenaka K et al. Anticancer molecular mechanism of 3'-ethynylcytidine (ECyd). In Nucleic acids research. Supplement (2001). 1 ed. 2001. p. 233-234
Wataya, Y. ; Futagami, M. ; Naito, T. ; Uchikubo, Y. ; Yokogawa, T. ; Takenaka, K. ; Kim, Hye-Sook ; Matsuda, A. ; Fukushima, M. ; Kitade, Y. / Anticancer molecular mechanism of 3'-ethynylcytidine (ECyd). Nucleic acids research. Supplement (2001). 1. ed. 2001. pp. 233-234
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