Study of ER stress mechanism which involved in cell death induced by a novel Golgi inhibitor M-COPA

2015 Fiscal Year Final Research Report

• Project/Area Number: 26830120
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: Akatsuka Akinobu 公益財団法人がん研究会, その他部局等, 研究員 (30649364)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 分子標的治療 / ゴルジ体 / 小胞体ストレス / 抗がん剤

Outline of Final Research Achievements

We previously identified M-COPA as a novel antitumor compound that seemed to have similar biological activities to Brefeldin A (BFA), a prototypic Golgi inhibitor, by using our original drug database screening system. Like BFA, M-COPA disrupted the Golgi apparatus and finally suppressed tumor cell proliferation in vivo. However, we have not yet elucidated the mechanism by which M-COPA exerts antitumor effect. Since BFA was shown to induce ER stress, we examined the activation of ER stress signals after exposure to M-COPA in vitro. Expectedly, M-COPA upregulated ER stress in tumor cells. On the other hand, human breast cancer BSY-1 cells, a M-COPA sensitive cell line, showed intensive ER stress response in vivo. In addition, shRNA knockdown of a ER stress suppressor BiP on human colon adenocarcinoma HT-29 cells, a M-COPA resistant cell line, induced sensitization to M-COPA. These results suggested the involvement of ER stress signal in the in vivo antitumor activity of M-COPA.

Free Research Field

腫瘍生物学