A FOXC2 inhibitor, MC-1-F2, as a therapeutic candidate for targeting EMT in castration-resistant prostate cancer
- Bioorg Med Chem Lett. 2023 Jul 15;91:129369. doi: 10.1016/j.bmcl.2023.129369.
- 1. Department of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, TX, USA.
- 2. Department of Chemistry and Biochemistry, The University of Texas at Tyler, Tyler, TX, USA.
- 3. Fisch College of Pharmacy, The University of Texas at Tyler, Tyler, TX, USA.
- 4. Sonora High School, La Habra, CA, USA.
- 5. Department of Chemistry and Biochemistry, The University of Texas at Tyler, Tyler, TX, USA. Electronic address: [email protected].
Androgen deprivation therapy (ADT) is the major treatment option for advanced prostate Cancer. However, prostate Cancer can develop into androgen-independent castration-resistant prostate Cancer (CRPC) which is resistant to ADT. An alternative treatment strategy for CRPC can be targeting the epithelial-mesenchymal transition (EMT). EMT is governed by a series of transcription factors of which forkhead box protein C2 (FOXC2) is a central mediator. Our previous research into the inhibition of FOXC2 in breast Cancer cells lead to the discovery of MC-1-F2, the first direct inhibitor of FOXC2. In current study on CRPC, MC-1-F2 has shown a decrease in mesenchymal markers, inhibition of Cancer stem cell (CSC) properties and decrease in invasive capabilities of CRPC cell lines. We have also demonstrated a synergistic effect between MC-1-F2 and docetaxel treatments, leading to a decrease in docetaxel dosage, suggesting the possible combination therapy of MC-1-F2 and docetaxel for the effective treatment of CRPC.