Allicin activates ER stress-induced IRE1α-JNK pathway and apoptosis via caspase-3/9 in BT-549 cell line

Breast cancer continues to represent a major contributor to cancer-related mortality, creating a severe public health burden worldwide. Adjuvant therapy is essential for nearly fifty percent of breast cancer patients following surgery to mitigate recurrence. Consequently, the use of effective chemotherapeutic agents to suppress tumor progression is a viable strategy for the management of breast cancer patients. Therefore, this study investigates the effects of allicin, a natural compound derived from garlic, on BT-549 human breast cancer cells. Additionally, its molecular mechanisms in programmed cell death were evaluated using a series of biochemical and cellular assays. The results demonstrated that allicin induces caspase-dependent cell death in cancer cells and enhances apoptotic signaling, as seen by elevated caspase expression. Furthermore, allicin induces the expression of protein markers associated with endoplasmic reticulum (ER) stress and activates c-Jun NH2-terminal kinase (JNK), which correlates with increased levels of proapoptotic markers. These findings indicate the involvement of reactive oxygen species in regulating these signaling pathways. Moreover, treatment with a JNK-specific inhibitor (SP600125) markedly reduced the effects of allicin and inhibited apoptotic marker expression in BT-549 cancer cells. Our preliminary findings suggest that allicin acts as a pro-oxidant, regulating programmed cell death pathways in BT-549 cancer cells through ROS signaling.