Luteolin-based nanocomposites in cancer: rewiring oncogenic signaling and non-coding RNA networks to restore programmed cell death

Luteolin, a naturally occurring flavonoid abundant in vegetables and medicinal plants, is increasingly recognized for its anticancer potential through pleiotropic effects on cellular signaling and gene expression. Recent research highlights its capacity to modulate multiple oncogenic pathways, regulate microRNA (miRNA) networks, and improve therapeutic efficacy when delivered via engineered nanocomposites. This narrative review critically evaluates current evidence on the molecular mechanisms by which luteolin interferes with cancer hallmarks. Particular focus is given to its influence on intracellular signaling cascades, miRNA regulation, and the development of nanocarrier-based delivery strategies. Literature was retrieved from PubMed, Scopus, and Web of Science up to October 2025, with selection based on relevance to cancer-related signaling pathways, miRNA modulation, and nanomedicine. Key mechanistic insights and experimental findings are synthesized into structured tables and pathway illustrations. Luteolin was found to suppress cancer progression through modulation of the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR), Janus kinase/signal transducer and activator of transcription (JAK/STAT), Wnt/β-catenin, and Notch signaling pathways, and to restore apoptosis sensitivity through tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated mechanisms. It also regulates oncogenic and tumor-suppressive miRNAs including miR-34a, miR-203, and let-7c. Moreover, folic acid-conjugated oxidized alpha-cyclodextrin (FA-Oxi-αCD) nanoparticle formulations significantly enhance luteolin’s bioavailability and tumor-specific delivery. In summary, luteolin represents a promising multi-targeted anticancer agent. Its rational incorporation into nanocomposite drug delivery systems may overcome existing clinical limitations and warrants further translational and clinical investigation.