Citrus limon Phytochemicals and Nanoparticle-Based Strategies in Prostate Cancer Models: Mechanistic Insights and Translational Perspectives

Abstract

Prostate cancer remains a major cause of cancer-related morbidity and mortality, while treatment resistance and adverse effects continue to limit therapeutic outcomes. Citrus limon contains diverse bioactive compounds, including flavonoids, limonoids, vitamin C, and volatile terpenes, with reported anticancer activities. This narrative review evaluates the available evidence on Citrus limon phytochemicals and nanoparticle-based strategies in prostate cancer, with emphasis on molecular mechanisms and translational limitations. Direct prostate-specific studies indicate that hesperidin can modulate proliferation in androgen-dependent and androgen-independent prostate cancer models. Citrus-derived obacunone has demonstrated effects on Akt, androgen receptor, prostate-specific antigen, apoptosis, and metabolic pathways in prostate cancer cells. Additional mechanisms reported across the evidence base include mitochondrial dysfunction, oxidative stress, calcium dysregulation, PI3K/Akt and MAPK signaling, and inflammatory pathway modulation. Evidence from non-prostate cancer models provides supportive mechanistic context but should not be interpreted as direct evidence of prostate cancer efficacy. Nanoparticle-based delivery may improve the stability, solubility, cellular uptake, and systemic exposure of citrus phytochemicals; however, direct evidence for Citrus limon-based nanoparticles in prostate cancer remains limited. Most prostate-specific studies are in vitro, with limited in vivo validation, pharmacokinetic data, and evidence regarding clinically achievable concentrations. Therefore, current findings support the preclinical and mechanistic potential of selected Citrus limon phytochemicals but do not establish clinical efficacy.