Diallyl Disulfide Inhibits Breast Cancer Stem Cell Progression and Glucose Metabolism by Targeting CD44/PKM2/AMPK Signaling

Background: It has been reported that diallyl disulfide (DADS) has anti-proliferative activity in many cancers. Objective: The purpose of this study was to investigate the functions of DADS and the underlying mechanisms of its effect in breast cancer stem cells (BCSCs). Method: Mammosphere formation assay, glucose consumption assay, lactate production assay and mouse xenograft experiments were performed to explore the functions of DADS in BCSCs. ATPase activity assay, western blotting and immunohistochemistry (IHC) assay were conduct to explore the mechanisms underlying the effects of DADS in BCSCs. Results: The results showed that DADS suppressed cell stemness and glucose metabolism in BCSCs. In vivo mouse xenograft experiments showed that DADS inhibited the proliferation and metastasis of BCSCs. Then, we continued to explore the mechanisms underlying the effects of DADS in BCSCs and found that DADS acts by targeting CD44, Pyruvate kinase M2 (PKM2) and AMP-activated protein kinase (AMPK) signaling pathways. IHC analysis of 125 breast cancer patients' tissues demonstrated that CD44, PKM2 and AMPK expression levels were positively correlated. In addition, positive CD44, PKM2 and AMPK expression was associated with poor patient overall survival (OS) and disease-free survival (DFS). Conclusion: In summary, DADS suppresses cell stemness, proliferation, metastasis and glucose metabolism in BCSCs partly through the inhibition of CD44/PKM2/AMPK. DADS may be used as a potential therapy for breast cancer treatment.