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Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)
ISSN (Print): 1871-5206
ISSN (Online): 1875-5992
Epub Abstract Ahead of Print
DOI: 10.2174/1871520614666140207154351      Price:  $95









Hypersensitivity to Aurora Kinase Inhibitors in Cells Resistant against Platinum-Containing Anticancer Agents

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Author(s): Masaki Akiyama, Hiroto Izumi, Wang Ke-Yong, Takahiro Yamaguchi, Akihiro Kuma, Noriaki Kitamura, Yoshikazu Harada, Ryoichi Oya, Koji Yamaguchi, Yoshiko Iwai and Kimitoshi Kohno
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Abstract:
The aurora kinases are serine/threonine kinases that are essential for mitosis and con-tribute to tumorigenesis. Therefore, aurora kinases hold promise for molecularly tar-geted therapy. In the present study, we demonstrated that aurora B kinase(AURKB) is overexpressed in both cisplatin- and oxaliplatin-resistant cells. Downregulation of AURKB sensitized cells to both cisplatin and oxaliplatin, but not to paclitaxel, 5-FU or hydrogen peroxide. Interestingly, we found that both cisplatin- and oxali-platin-resistant cells were hypersensitive to the AURKB specific inhibitors, AZD1152 HQPA and ZM447439, suggesting that both cisplatin- and oxaliplatin-resistant cells develop an addiction to AURKB. These data provide evidence that aurora kinase inhibitors can overcome both cisplatin and oxaliplatin resistance. Therefore, AURKB inhibitors could offer potential benefits if used after first-line platinum-based chemo-therapy
Affiliation:
The President Laboratory, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555 , Japan