Anticancer mechanisms of 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl) cytosine (ECyd, TAS-106).

Tomoharu Naito, Tatsushi Yokogawa, Hey Sook Kim, Michiko Futagami, Yusuke Wataya, Akira Matsuda, Masakazu Fukushima, Yukio Kitade, Takuma Sasaki

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

We investigated the molecular mechanisms of cell death induced by 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd, TAS-106), a potent inhibitor of RNA synthesis, using mouse mammary tumor FM3A cells and human fibrosarcoma HT1080 cells. ECyd induced the characteristics of apoptosis on these cells, such as morphological changes, DNA fragmentations and caspase-3-like protease activation. General caspases inhibitor, Z-Asp-CH2-DCB inhibited cell death. Interestingly, we also found that ECyd induced rRNA fragmentation. The cleavage pattern of rRNA resembled in that mediated by RNase L. On the other hands, it was suggested that caspase-1, 3, 8 and 9 concerned with ECyd-induced apoptosis through mitochondria. ECyd-induced rRNA fragmentation was inhibited by general caspases inhibitor (Z-Asp-CH2-DCB) and caspase-5 inhibitor (Z-WEHD-fmk). So it is clear that caspase-5 (ICErel III/TY), member of ICE (Interleukin-1 beta-converting enzyme) protease, activated pathway concerned with ECyd-induced rRNA fragmentation. These results indicate that antitumor mechanisms of ECyd are involved in caspase-dependent activation of RNase L. rRNA fragmentation may occur one of the death events, as a result of inhibition of RNA synthesis and play an important role in the antitumor activity of ECyd.

Original languageEnglish
Pages (from-to)241-242
Number of pages2
JournalNucleic acids research. Supplement (2001)
Issue number2
Publication statusPublished - 2002

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Anticancer mechanisms of 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl) cytosine (ECyd, TAS-106).'. Together they form a unique fingerprint.

  • Cite this

    Naito, T., Yokogawa, T., Kim, H. S., Futagami, M., Wataya, Y., Matsuda, A., Fukushima, M., Kitade, Y., & Sasaki, T. (2002). Anticancer mechanisms of 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl) cytosine (ECyd, TAS-106). Nucleic acids research. Supplement (2001), (2), 241-242.