Discovering alkylamide derivatives of bexarotene as new therapeutic agents against triple-negative breast cancer

Bioorg Med Chem Lett. 2018 Feb 1;28(3):420-424. doi: 10.1016/j.bmcl.2017.12.033.

Luxi Chen ¹, Chao Long ¹, Jennifer Nguyen ¹, Dhiraj Kumar ¹, Jiyong Lee ²

Affiliations

1 Department of Chemistry and Biochemistry, The University of Texas at Dallas, 800 W. Campbell Rd., Richardson, TX 75080, USA.
2 Department of Chemistry and Biochemistry, The University of Texas at Dallas, 800 W. Campbell Rd., Richardson, TX 75080, USA. Electronic address: jiyong.lee@utdallas.edu.

PMID: 29287960 DOI: 10.1016/j.bmcl.2017.12.033

Abstract

Triple-negative breast Cancer (TNBC) has been reported to be correlated with high expression of proliferation markers as well as constitutive activation of metastasis-relevant signaling pathways. For many years, breast Cancer researchers have been investigating specific and effective methods to treat or to control the development of TNBC, but promising therapeutic options remain elusive. In this study, we have demonstrated that alkylamide derivatives of bexarotene DK-1-150 and DK-1-166 induce apoptotic cell death in TNBC cell lines without causing cytotoxicity in the normal mammary epithelial cell line. Furthermore, the bexarotene derivatives also showed significant effects in inhibiting TNBC cell proliferation and migration, modulating Cancer stem cell markers expressions, as well as limiting the epithelial-mesenchymal transition (EMT) activities of TNBC cell lines in terms of downregulating EMT marker and blocking nuclear translocation of β-catenin. Therefore, we propose the alkylamide derivatives of bexarotene as potential candidates for novel Anticancer therapeutics against TNBC.

Keywords

Anti-cancer therapeutics; Apoptosis; Cancer stem cell; Epithelial-mesenchymal transition; Triple-negative breast cancer.

Name
Email *

	Sorry, but the email address you supplied was invalid.