Study of ER stress mechanism which involved in cell death induced by a novel Golgi inhibitor M-COPA
| Project/Area Number |
26830120
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor therapeutics
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| Research Institution | Japanese Foundation for Cancer Research |
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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)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 分子標的治療 / ゴルジ体 / 小胞体ストレス / 抗がん剤 / 分子標的薬 |
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| 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.
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Report
(3 results)
Research Products
(12 results)
