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The zinc complex of 3,5-di-tert-butyl salicylate (Zn{[CH 3 ) 3 C] 2 Sal} 2  2− ) 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{[CH 3 ) 3 C] 2 Sal} 2  2−  treatment. Further GO and KEGG analysis showed that the activity of Zn{[CH 3 ) 3 C] 2 Sal} 2  2−  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{[CH 3 ) 3 C] 2 Sal} 2  2−  treatment, as demonstrated by western blot. Our results indicate that Zn{[CH 3 ) 3 C] 2 Sal} 2  2−  inhibits the activity of TNBC cells by downregulating the STAT3 signaling through the SRC pathway.

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