Dual Role of Diallyl Disulfide (DADS) on Invasive Potential and β-Catenin Dynamics in HER2-Positive Breast Cancer Cells

<b>Background/Objectives:</b> Natural compounds are being increasingly explored as potential adjuvants to conventional drugs in oncological treatments. Regarding breast tumors, several studies indicate that garlic (<i>Allium sativum</i>) may protect against onset, counteracts aggressiveness, and prevents malignant progression of cells from non-invasive tumors. It has been widely demonstrated that garlic derivatives induce apoptosis and reduce invasive potential in ER-positive and triple-negative breast tumor cells. However, the current literature lacks studies investigating their effects on HER2-positive (HER2+) breast cancers. This study therefore aimed to explore the effects of a garlic extract and diallyl disulfide (DADS), one of its most bioactive organosulfur compounds, on HER2+ phenotype breast tumor cells. <b>Methods:</b> The effects of a garlic extract and diallyl disulfide (DADS) were investigated on MDA-MB-453 and SKBR3 breast tumor cell lines. Cell growth, invasive potential, and Akt-related signaling were assessed after 4-72 h of garlic derivatives administration. The intracellular localization of β-catenin was examined with immunofluorescent confocal microscopy. <b>Results:</b> A dual role of DADS, dependent on the duration of treatment, was revealed. Acute administration induced a significant decrease in invasive potential, while prolonged treatment promoted HER2+ cell invasiveness. These effects were directly correlated with the activation of Akt and the nuclear accumulation of β-catenin, known to induce expression of genes associated with tumor malignancy. <b>Conclusions:</b> Although further investigations are needed to establish the exact mechanism and to assess the in vivo reproducibility of these phenomena, our results highlight the heterogeneous response to natural compounds of complex diseases like cancer.