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

Abstract

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. CoIII-Ebox is a cobalt(III) complex attached to an Ebox oligonucleotide that confers specificity towards Snail TFs. CoIII-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 CoIII-Ebox in inhibiting the invasive aspects of heregulin β1(HRG)-treated breast cancer cells. CoIII-Ebox was found to inhibit the capacity of Snail to repress target genes after HRG induction. Snail inhibition by CoIII-Ebox reduced the invasive propensity of cells in 2D and 3D, thereby demonstrating promise in inhibiting metastasis.

Epithelial‐mesenchymal transition inducer Snail1 and invasive potential of intraductal breast cancer

“…Among new predictive biomarkers of aggressive DCIS, Snail1 seems a promising one. Most recent studies suggest that Snail1 suppression can reduce invasive propensity of breast cancer cells . Moreover, some drugs and anti‐tumor agents have been reported to inhibit EMT by down‐regulation of Snail1 signaling pathway, which results in anti‐metastatic effect .…”

Epigenetic Regulation and Post-Translational Modifications of SNAI1 in Cancer Metastasis

“…A Co(III) complex conjugated to a CAGGTG hexanucleotide was synthesized. This complex binds to SNAI1 and prevents any interaction with DNA, thus reducing the invasive potential of tumor cells [93]. Second, the SNAI1-p53 complex acts as a target.…”

Propolin G-Suppressed Epithelial-to-Mesenchymal Transition in Triple-Negative Breast Cancer Cells via Glycogen Synthase Kinase 3β-Mediated Snail and HDAC6-Regulated Vimentin Degradation

“…Furthermore, Snail expression is decidedly associated with tumor grade, nodal metastasis of invasive ductal carcinoma, and outcome prediction of breast cancer [48,51,52]. Blockade of Snail expression or activity is targeted to restrain EMT and cancer metastasis [53][54][55]. The role of Snail in propolin G-suppressed migration and invasion in MDA-MB-231 cells was appraised because propolin G-inhibited Snail expression had been observed in MDA-MB-231 cells through a dose-and time-dependent model (Figure 3 A,B).…”