RRC ID 69234
Author Sato H, Yamada R, Yanagihara M, Okuzawa H, Iwata H, Kurosawa A, Ichinomiya S, Suzuki R, Okabe H, Yano T, Kumamoto T, Suzuki N, Ishikawa T, Ueno K.
Title New 2-aryl-1,4-naphthoquinone-1-oxime methyl ether compound induces microtubule depolymerization and subsequent apoptosis.
Journal J Pharmacol Sci
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 G(2)/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-G(1) 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 time-dependently after QO-1 exposure. In conclusion, QO-1 has promising antitumor effects via microtubule depolymerization.
Volume 118(4)
Pages 467-78
Published 2012-1-1
DOI 10.1254/jphs.11229fp
PMID 22447301
MeSH Apoptosis / drug effects* Apoptosis / physiology Cell Cycle / drug effects Cell Cycle / physiology Cell Line, Tumor DNA Fragmentation / drug effects HeLa Cells Humans Methyl Ethers / chemistry Methyl Ethers / pharmacology Microtubules / drug effects* Microtubules / metabolism Naphthoquinones / chemistry* Naphthoquinones / pharmacology* Tubulin Modulators / chemistry Tubulin Modulators / pharmacology*
IF 2.835
Human and Animal Cells HeLa(RCB0007)