Targeted Inhibition of Snail Activity in Breast Cancer Cells by Using a Co^III-Ebox Conjugate

The transition from a non-invasive to an invasive phenotype is an essential step in tumor metastasis. The Snail family of transcription factors (TFs) is known to play a significant role in this transition. These TFs are zinc fingers that bind to the CAGGTG Ebox consensus sequence. Co^III-Ebox is a cobalt(III) complex attached to an Ebox oligonucleotide that confers specificity towards Snail TFs. Co^III-Ebox has been shown to inhibit Snail-mediated embryonic neural crest development in Xenopus laevis, but its efficacy in inhibiting Snail-induced cancer cell invasiveness has not been explored. Here, we describe the efficacy of Co^III-Ebox in inhibiting the invasive aspects of heregulin-β1(HRG)-treated breast cancer cells. Co^III-Ebox was found to inhibit the capacity of Snail to repress target genes after HRG induction. Snail inhibition by Co^III-Ebox reduced the invasive propensity of cells in 2D and 3D, thereby demonstrating promise in inhibiting metastasis.