Role of diosgenin in gastrointestinal cancers: recent trends and future perspectives

Gastrointestinal cancers represent a considerable global public health burden, due to their high incidence, poor prognosis, and resistance to conventional therapies. Traditional treatments like chemotherapy and radiation often produce side effects and limited efficacy, making targeted therapies even more necessary. Diosgenin, a naturally steroidal saponin found in Dioscorea species, has gained widespread acclaim as an anticancer agent due to its anti-inflammatory, antioxidant, and cancer-fighting properties. This review presents an organ-specific assessment of diosgenin's anticancer properties against various gastrointestinal cancers, such as esophageal, gastric, colorectal, pancreatic, and liver. Although numerous reviews have addressed diosgenin's anticancer potential, ours stands out by offering an in-depth disease-specific mechanistic analysis, while taking advantage of recent advances in nanotechnology for optimizing its pharmacokinetics and bioavailability. Key highlights include diosgenin's synergistic interactions with cancer pathways such as Wnt/b-catenin, STAT3, and NF-kB—aspects not fully examined in previous reviews. Diosgenin's potential use in combination therapies with chemotherapeutics is also explored, including its clinical readiness as well as potential challenges such as bioavailability and solubility. Diosgenin has shown significant promise in preclinical studies; however, human cancer therapies require clinical trials to ascertain its safety and efficacy in human cancer treatments. This review offers a comprehensive perspective of diosgenin's mechanisms, nanomedicine innovations, and translational prospects—representing an essential step toward understanding its role in gastrointestinal cancers.