Aurintricarboxylic acid, an inhibitor of cystathionine γ-lyase, enhances the sensitivity of chemotherapy drugs in TNBC

The current treatments for triple-negative breast cancer (TNBC) rely mainly on chemotherapy. Enhancing the effect of chemotherapy drugs or exploring new targeted drugs is expected to provide more treatment options for patients with TNBC. Our previous studies have shown that the cystathionine-γ-lyase (CSE) plays an important role in the progression of TNBC. So inhibition of CSE may provide a new direction for the treatment of TNBC. This study aimed to explore the relationship between CSE expression and chemotherapy drug sensitivity, as well as the potential therapeutic role of CSE inhibitor Aurintricarboxylic acid (ATA) in TNBC. The results suggest that the expression of CSE is negatively correlated with the sensitivity of chemotherapy drugs and changes in CSE levels affect the sensitivity of chemotherapy drugs in TNBC cells. The CSE inhibitor ATA has significantly enhanced the sensitivity of chemotherapeutic drugs in MDA-MB-231 cells and 4T1 mouse transplanted tumor model. Further mechanism research has found that ATA enhances the sensitivity of chemotherapeutic drugs via SIRT1-STAT3-C-myc-Bcl-2 signaling pathway in TNBC cells. In addtion, ATA also enhances the sensitivity of chemotherapeutic drugs in TNBC cells by regulating the expression of P-glycoprotein (P-gp), glutathione (GSH) and reactive oxygen species (ROS). These findings suggest that ATA may be a promising therapeutic agent for TNBC treatment by enhancing the sensitivity of chemotherapy drugs through multiple mechanisms.