2. Academic Validation
  3. Wnt/β-Catenin Small-Molecule Inhibitor CWP232228 Preferentially Inhibits the Growth of Breast Cancer Stem-like Cells

Wnt/β-Catenin Small-Molecule Inhibitor CWP232228 Preferentially Inhibits the Growth of Breast Cancer Stem-like Cells

  • Cancer Res. 2015 Apr 15;75(8):1691-702. doi: 10.1158/0008-5472.CAN-14-2041.
Gyu-Beom Jang 1,  In-Sun Hong 1,  Ran-Ju Kim 1,  Su-Youn Lee 1,  Se-Jin Park 1,  Eun-Sook Lee 2,  Jung Hyuck Park 3,  Chi-Ho Yun 3,  Jae-Uk Chung 3,  Kyoung-June Lee 3,  Hwa-Yong Lee 4,  Jeong-Seok Nam 5
Affiliations

Affiliations

  • 1 Laboratory of Tumor Suppressor, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, South Korea. Department of Molecular Medicine, School of Medicine, Gachon University, Incheon South Korea.
  • 2 Division of Convergence Technology, Center for Breast Cancer, Research Institute and Hospital, National Cancer Center 323, Ilsan-ro, Ilsandong-gu, Goyang-si Gyeonggi-do, South Korea.
  • 3 JW Pharmaceutical, 2477 Nambusunhwan-ro, Seocho-gu, Seoul, South Korea.
  • 4 The Faculty of Liberal Arts, Jungwon University, Chungbuk, Republic of Korea.
  • 5 Laboratory of Tumor Suppressor, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, South Korea. Department of Molecular Medicine, School of Medicine, Gachon University, Incheon South Korea. namjs@gachon.ac.kr.
PMID: 25660951 DOI: 10.1158/0008-5472.CAN-14-2041
Abstract

Breast Cancer Stem Cells (BCSC) are resistant to conventional chemotherapy and radiotherapy, which may destroy tumor masses but not all BCSC that can mediate relapses. In the present study, we showed that the level of Wnt/β-catenin signaling in BCSC is relatively higher than in bulk tumor cells, contributing to a relatively higher level of therapeutic resistance. We designed a highly potent small-molecule inhibitor, CWP232228, which antagonizes binding of β-catenin to T-cell factor (TCF) in the nucleus. Notably, although CWP232228 inhibited the growth of both BCSC and bulk tumor cells by inhibiting β-catenin-mediated transcription, BCSC exhibited greater growth inhibition than bulk tumor cells. We also documented evidence of greater insulin-like growth factor-I (IGF-I) expression by BCSC than by bulk tumor cells and that CWP232228 attenuated IGF-I-mediated BCSC functions. These results suggested that the inhibitory effect of CWP232228 on BCSC growth might be achieved through the disruption of IGF-I activity. Taken together, our findings indicate that CWP232228 offers a candidate therapeutic agent for breast Cancer that preferentially targets BCSC as well as bulk tumor cells.

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