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.

Breast cancer is the most commonly diagnosed cancer among women, with approximately one in eight women developing the disease during their lifetime. Despite advancements in current treatment options, breast cancer was responsible for an estimated 670,000 deaths worldwide in 2022. This highlights the urgent need for the development of novel therapeutic strategies. Historically, plant-derived compounds have played a significant role in cancer therapy, exemplified by widely used chemotherapeutic agents such as paclitaxel and docetaxel. In recent years, increasing attention has been directed toward novel plant-derived compounds as potential anti-cancer agents. Among these, Naringenin, a flavonoid predominantly found in citrus fruits, has shown promising antioxidant, anti-inflammatory, and anti-cancer properties. This review highlights recent studies investigating the effects of Naringenin and its derivatives on breast cancer. Evidence from both in vitro and in vivo animal models suggests that Naringenin may exert anti-tumor activity by inhibiting cell proliferation, promoting apoptosis, modulating key cell signaling pathways, and enhancing radio-sensitivity in breast cancer cells. Although preclinical evidence strongly supports the anticancer potential of Naringenin in breast cancer, comprehensive clinical studies are urgently needed to validate its efficacy and safety in humans.