122nd General Meeting of the KCS

Type Poster Presentation
Area Life Chemistry
Room No. Grand Ballroom
Time 10월 19일 (금요일) 11:00~12:30
Code LIFE.P-411
Subject Homoharringtonine induces apoptosis in human colorectal carcinoma HCT116 cells via downregulation of Wnt/β-catenin signaling cascade
Authors Mikyung Park, Ho Jeong Kwon1, Seong Hwan Kim2,*
Department of Biotechnology, Yonsei University / Innovative Target Research Center, Korea
1Department of Biotechnology, Yonsei University, Korea
2Innovative Target Research Center, Korea Research Institute of Chemical Technology, Korea
Abstract The Wnt/β-catenin pathway plays an important role in cancer development. Since β-catenin is one of main factors for the survival of colon cancers through maintaining the efficient activation of Wnt-responsive genes such as c-Myc and cyclin D1, the targeting of β-catenin could be a promising approach for treating colon cancers. Therefore, we screened 9,939 compounds and identified homoharringtonine (HHT) as the most potentially active compound to inhibit β-catenin activity. HHT reduced the protein levels of c-Myc and cyclin D1, demonstrating its potential to inhibit β-catenin activity. Time-dependent experiments also suggested that its potential to inhibit β-catenin activity could lead to the caspase-dependent apoptotic death of human colorectal carcinoma HCT116 cells. Inhibitory activity of HHT on the growth of HCT116 cells was also confirmed in colony formation experiment. Notably, among the signaling factors in Wnt signaling and secretion, HHT reduced the expression levels of p-LRP6, LRP, β-catenin, TCF4 and porcupine, but not Dvl, demonstrating that HHT exhibits anti-colon cancer action via inhibiting β-catenin activity. Considering that HHT is being clinically used for treating patients with chronic myeloid leukemia, these results warrant its development as a potential anti-cancer drug targeting colon cancers.
E-mail whdhwhdh@naver.com