Zinc complex of 3,5-di-tert-butyl salicylate inhibits viability, migration, and invasion in triple-negative breast cancer cells.

The zinc complex of 3,5-di-tert-butyl salicylate (Zn{[CH3)3C]2Sal}22-) is a zinc ion chelate of salicylate. In this study, we found that this compound inhibits viability, invasion, and migration and induces apoptosis in triple-negative breast cancer 4T1 cells. RNA-seq showed that the expression of 17 genes was upregulated and 26 genes were downregulated significantly by Zn{[CH3)3C]2Sal}22- treatment. Further GO and KEGG analysis showed that the activity of Zn{[CH3)3C]2Sal}22- against triple-negative breast cancer cells may be involved in the JAK-STAT3, HIF-1, and TNF signaling pathways. The expression of key genes was verified by RT-PCR. The phosphorylation of STAT3 and its upstream SRC decreased drastically upon Zn{[CH3)3C]2Sal}22- treatment, as demonstrated by western blot. Our results indicate that Zn{[CH3)3C]2Sal}22- inhibits the activity of TNBC cells by downregulating the STAT3 signaling through the SRC pathway.