Lycopene-Mediated Modulation of Apoptosis and Survival Signalling in Cancer: Emerging Nanodelivery Strategies and Translational Limitations

Lycopene is a dietary carotenoid with anti-inflammatory, proapoptotic, antiproliferative, and antioxidant properties in cancer models. Its application is limited by poor solubility, inconsistent bioavailability, formulation challenges, and unclear mechanisms of action. This review explores the mechanistic, preclinical, and clinical evidence of lycopene’s involvement in cell death and survival pathways, considering experimental models, mechanistic specificity, relevance, pharmacokinetics, and clinical validation. The most supported mechanism is mitochondrial apoptosis, indicated by a higher BAX/BCL-2 ratio, mitochondrial disruption, cytochrome c release, and caspase activation. Evidence on autophagy is mixed, with no proof that it causes cancer cell death. Human studies are limited and heterogeneous, primarily using tomato products or purified lycopene, and have demonstrated exposure and tolerability but not anticancer effects. One phase I trial found that synthetic lycopene was well tolerated, with some pharmacokinetic and biomarker changes but showed limited efficacy when combined with docetaxel. In vitro, nanocarriers enhance lycopene’s dispersion, stability, and tumour targeting, although data on pharmacokinetics, biodistribution, manufacturing, and safety remain limited. Currently, lycopene is an investigational agent for cancer prevention rather than an approved therapy; existing conclusions relate to other uses. Progressing towards clinical application requires developing standardised formulations, confirming exposure in models, and designing appropriate clinical trials.