Curcumin as a ceramide metabolism-targeting agent: Molecular mechanisms and therapeutic implications in cancer

Curcumin, a lipophilic polyphenol widely used in traditional medicine, is the active ingredient in turmeric (Curcuma longa L.). It has various therapeutic effects, such as antitumor potential, due to its interaction with intracellular and extracellular molecules associated with different malignancies. Ceramides are fundamental constituents of cellular membranes that maintain the stability and integrity of cells. Additionally, they have become key signaling agents that govern a spectrum of cellular functions, such as differentiation, proliferation, apoptosis, and cellular senescence. This review primarily introduces ceramides and their metabolism, summarizes their crucial roles in cancer, and categorizes and discusses the mechanisms and pathways through which curcumin could potentially exert its antitumor effects by targeting ceramides. These mechanisms include apoptosis- and autophagy-associated pathways, de novo ceramide generation, and influencing intracellular free calcium levels and acid inhibition. ceramidase, and combinational strategies using various chemical agents, ceramides, or ceramide analogs to enhance curcumin's efficacy. Finally, the review concludes with remarks and prospects for the future of curcumin's antitumor potential in the context of ceramide targeting.