New 2-Aryl-1,4-naphthoquinone-1-oxime Methyl Ether Compound Induces Microtubule Depolymerization and Subsequent Apoptosis

Journal of Pharmacological Sciences

Midori Yanagihara⁴  Ayako Kurosawa³  Hiromi Sato⁴  Noriyuki Suzuki³  Koichi Ueno⁴  Saki Ichinomiya⁴  Tomohiro Yano²  Takuya Kumamoto¹  Tsutomu Ishikawa³  Hiroyuki Okabe⁴  Hiroko Okuzawa⁴  Ryota Yamada⁴  Hiroki Iwata⁴  Rina Suzuki⁴ 

[1] Faculty of Pharmaceutical Sciences, Musashino University, Japan;Department of Life Environmental Sciences, Faculty of Life Sciences, Toyo University, Japan;Department of Medicinal Organic Chemistry, Graduate School of Pharmaceutical Sciences, Chiba University, Japan;Department of Geriatric Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Chiba University, Japan

关键词: naphthoquinone-1-oxime;    microtubule depolymerization;    cytotoxicity;    spindle assembly checkpoint;    cell cycle;   

DOI  :  10.1254/jphs.11229FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(43)Cited-By(1)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 time-dependently after QO-1 exposure. In conclusion, QO-1 has promising antitumor effects via microtubule depolymerization.

【 授权许可】

Unknown