Potential new chemotherapy strategy for human ovarian carcinoma with a novel KSP inhibitor

被引：6

作者：

Takenaga, Mitsuko ^{[1
]}

Yamamoto, Yuki ^{[1
]}

Takeuchi, Tomoki ^{[2
]}

Ohta, Yuki ^{[3
]}

Tokura, Yukie ^{[1
]}

Hamaguchi, Akemi ^{[1
]}

Asai, Daisuke ^{[4
]}

Nakashima, Hideki ^{[4
]}

Oishi, Shinya ^{[2
]}

Fujii, Nobutaka ^{[2
]}

机构：

[1] St Marianna Univ, Sch Med, Inst Med Sci, Miyamae Ku, Kawasaki, Kanagawa 2168512, Japan

[2] Kyoto Univ, Grad Sch Pharmaceut Sci, Sakyo Ku, Kyoto 6068501, Japan

[3] St Marianna Univ, Sch Med, Dept Pharmacol, Miyamae Ku, Kawasaki, Kanagawa 2168512, Japan

[4] St Marianna Univ, Sch Med, Dept Microbiol, Miyamae Ku, Kawasaki, Kanagawa 2168512, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2015年 / 463卷 / 03期

关键词：

Apoptosis; Kinesin spindle protein; Human ovarian cancer; Neurotoxicity; Securin; KINESIN SPINDLE PROTEIN; DOSE-ESCALATION; CANCER-CELLS; ARRY-520; EG5; DERIVATIVES; PACLITAXEL; SCAFFOLDS; MECHANISM; ISPINESIB;

D O I：

10.1016/j.bbrc.2015.05.029

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Among synthetic kinesin spindle protein (KSP) inhibitor compounds, KPYB10602, a six-member lactam-fused carbazole derivative was the most potent in vitro against cell growth of human ovarian cancer, A2780. KPYB10602 caused dose-dependent suppression of tumor growth in vivo. mitotic arrest due to KPYB10602 was confirmed in vitro, and was characterized by inhibition of securin degradation. Apoptosis after mitotic arrest was associated with an increase in the ratio of pro-apoptotic Bax to anti-apoptotic BcI-2. Increase of reactive oxygen species (ROS) and caspase pathway were also involved. Furthermore, KPYB10602 caused little neurotoxicity in vivo. Therefore, KPYB10602 could be a promising candidate as an anti-tumor agent with reduced adverse events for treating human ovarian cancer. (C) 2015 Elsevier Inc. All rights reserved.

引用

页码：222 / 228

页数：7

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