ASK1 in Cancer Cell Death: Insights from In Vitro and In Vivo Studies

Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase (MAP3K) involved in stress-induced apoptosis. Increasing evidence indicates that ASK1 activation contributes to the anticancer activity of numerous compounds, particularly those that induce oxidative or endoplasmic reticulum stress. This review summarizes studies demonstrating ASK1-dependent apoptosis in models of lung, breast and gynecologic, or gastrointestinal cancers following treatment with natural products, phytochemicals, and synthetic agents, focusing on mechanistic evidence linking ASK1 to downstream activation of the JNK and p38 MAPK pathways, mitochondrial dysfunction, and caspase-dependent cell death. Studies were selected based on direct experimental validation of ASK1 activation and involvement in the observed anticancer effects. Overall, this review supports ASK1 as a promising molecular target for the development of novel cancer treatment strategies.