16:00 - 18:00
Room: Poster Area - Poster Shed
Poster Presentation
A lignan induces lysosomal dependent degradation of FoxM1 protein to suppress β-catenin nuclear translocation
Ji Hye Jeong 1, Guang-zhi Dong 1, Yu-ih Lee 1, Yeong Eun Han 1, Jung Sook Shin 1, Yoon-Jung Kim 1, Raok Jeon 1, Young Hwa Kim 2, Tae Jun Park 2, Keun Il Kim 3, Jae-Ha Ryu 1
1 Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women’s University, Seoul
2 Department of Biochemistry and Molecular Biology, School of Medicine, Ajou University, Suwon
3 Department of Biological Science, Sookmyung Women’s University, Seoul

In this study, we isolated a lignan [(−)-(2R,3R)-1,4-O-diferuloylsecoisolariciresinol, DFS] from Alnus japonica (Betulaceae) and investigated its biological activity and mechanism of action on colon cancer. DFS reduced the viability of colon cancer cells and induced cell cycle arrest. DFS also suppressed β-catenin nuclear translocation and β-catenin target gene expression through a reduction in FoxM1 protein. To assess the mechanism of the action of DFS, we investigated the effect of DFS on endogenous and exogenous FoxM1 protein degradation in colon cancer cells. DFS-induced FoxM1 protein degradation was suppressed by lysosomal inhibitors, chloroquine and bafilomycin A1, but not by knock-down of proteasomal proteins. The mechanism of DFS for FoxM1 degradation is lysosomal dependent, which was not reported before. Furthermore, we found that FoxM1 degradation was partially lysosomal-dependent under normal conditions. These observations indicate that DFS from A. japonica suppresses colon cancer cell proliferation by reducing β-catenin nuclear translocation. DFS induces lysosomal-dependent FoxM1 protein degradation. This is the first report on the lysosomal degradation of FoxM1 by a small molecule. DFS may be useful in treating cancers that feature the elevated expression of FoxM1.


Reference:
Poster Session-PO-75:
Session:
Poster Presentation-1
Presenter/s:
Ji Hye Jeong
Presentation type:
Poster presentation
Room:
Poster Area - Poster Shed
Date:
Monday, 27th August, 2018
Time:
16:00 - 18:00
Session times:
16:00 - 18:00