Investigating the Anti-Tumor Effects of Two Novel B-Catenin Inhibitors in Ovarian Cancer Cells
Nguyen, Vu Hong Loan
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Epithelial ovarian cancer (EOC) is the deadliest female malignancy. The development of chemoresistance and relapse becomes a major challenge in treating ovarian cancer. The Wnt/-catenin pathway, which plays a critical role in developmental and physiological processes, have been indicated to contribute to EOC development. Aberrant activation of this pathway was reported to promote cancer stem cell self-renewal, metastasis, and chemoresistance in all subtypes of EOC, suggesting the Wnt/-catenin pathway is a strong candidate for the development of targeted therapies. In this study, we have identified and investigated the anti-tumor effects of two novel -catenin inhibitors, referred to as compound 2 (C2) and C10. Results from functional assays showed that C2 and C10 inhibited EOC cell proliferation, anchorage-independent growth, and spheroid formation. In addition, C10 treatment inhibited the expression of stem cell markers of EOC cells, suggesting the small molecule inhibitors target ovarian cancer stem cells. Using TOPflash reporter assays, we found that C2 and C10 inhibited the transcriptional activity of -catenin/TCF complex. Finally, preliminary results suggest that C2 and C10 bind directly to recombinant -catenin. Taken together, this study identified two novel potent -catenin inhibitors that have strong anti-tumor effects. These compounds could be potentially developed into targeted therapies for ovarian cancer patients who harbor abnormal activation of Wnt/-catenin signaling.