| 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)
|
|---|
| 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.
|
