Dataset Information

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. 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-?1(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.

SUBMITTER: Vistain LF

PROVIDER: S-EPMC4638217 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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

Vistain Luke F LF Yamamoto Natsuho N Rathore Richa R Cha Peter P Meade Thomas J TJ

Chembiochem : a European journal of chemical biology 20150825 14

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 Xenopu ...[more]

PMID: 26305708

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Project description:A class of phosphane gold(I) compounds, made of azoles and phosphane ligands, was evaluated for a screening on the regards of Breast Cancer cell panels (BC). The compounds possess N-Au-P or Cl-Au-P bonds around the central metal, and they differ for the presence of aprotic or protic polar groups in the azoles and/or the phosphane moieties to tune their hydrophilicity. Among the six candidates, only the compounds having the P-Au-N environment and not displaying neither the hydroxyl nor carboxyl groups in the ligands were found active. The compounds were screened by MTT tests in SKBR3, A17, and MDA-MB231 cancer cells, and two compounds (namely the 4,5-dicyano-imidazolate-1yl-gold(I)-(triphenylphosphane, 5, and 4,5-dichloro-imidazolate-1yl-gold(I)-triphenylphosphane, 6) were found very cytotoxic, with the most active with an IC50 value of 3.46 μM in MDA-MB231 cells. By performing enzymatic assays in the treated cells lysates, the residual enzymatic activity of dihydrofolate reductase (DHFR) has been measured after cell treatment for 4 or 12 h in comparison with control cells. Upon 12 h of treatment, the activity of DHFR was significantly reduced in both SKBR3 and A17 cells by compounds 5 and 6, but not in human MDA-MB231 cells; interestingly, it was found remarkably high after 4 h of treatment, revealing a time dependence for the DHFR enzymatic assays. The DHFR inhibition data have been compared to those for the thioredoxin reductase (TrxR), the most recognized molecular target for gold compounds. For this latter, similar residual activities (i.e., 37 and 49% for the match of SKBR3 cells and compound 5 or 6, respectively) were found. Binding studies on the regards of ct-DNA (calf-thymus-DNA) and of plasma transporters proteins, such as BSA (bovine serum albumin) and ATF (apo transferrin), were performed. As expected for gold compounds, the data support strong binding to proteins (Ksv values range: 1.51 ÷ 2.46 × 104 M-1) and a weaker interaction with ct-DNA's minor groove (Ksv values range: 1.55 ÷ 6.12 × 103 M-1).

Dataset Information

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

Publications

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

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