New 2-aryl-1,4-naphthoquinone-1-oxime methyl ether compound induces microtubule depolymerization and subsequent apoptosis

Hiromi Sato, Ryota Yamada, Midori Yanagihara, Hiroko Okuzawa, Hiroki Iwata, Ayako Kurosawa, Saki Ichinomiya, Rina Suzuki, Hiroyuki Okabe, Tomohiro Yano, Takuya Kumamoto, Noriyuki Suzuki, Tsutomu Ishikawa, Koichi Ueno

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

In this study, we describe the antitumor activity of QO-1, one of the new 2-aryl-1,4-naphthoquinone-1-oxime methyl ether derivatives. QO-1 is a derivative of macarpine, a natural occurring product from Rutaceae plant. It could potently inhibit cell growth when tested on 19 cancer cell lines. To investigate its mechanism, two cell lines (HeLa and MCF-7) sensitive to QO-1 were selected. Based on flow cytometry, it was found to induce G2/M-phase arrest. Moreover, it could cause microtubule depolymerization both in vitro and in vivo. On the other hand, QO-1 activated spindle assembly checkpoint (SAC) proteins. Expression of Bub1, one of the SAC, was gradually increased, reaching a peak after 16 - 20 h, and then gradually decreased. Instead, QO-1 increased the sub-G1 population, which suggested a cell death population. Actually, expression of Bcl-2 family proteins and activation of caspase-3/7 were evidences of apoptosis. Consistent with these results, cells with DNA fragmentation and multinucleated cells were increased timedependently after QO-1 exposure. In conclusion, QO-1 has promising antitumor effects via microtubule depolymerization.

Original languageEnglish
Pages (from-to)467-478
Number of pages12
JournalJournal of Pharmacological Sciences
Volume118
Issue number4
DOIs
Publication statusPublished - 2012
Externally publishedYes

Keywords

  • Cell cycle
  • Cytotoxicity
  • Microtubule depolymerization
  • Naphthoquinone-1-oxime
  • Spindle assembly checkpoint

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Fingerprint Dive into the research topics of 'New 2-aryl-1,4-naphthoquinone-1-oxime methyl ether compound induces microtubule depolymerization and subsequent apoptosis'. Together they form a unique fingerprint.

Cite this