Medical Science: Recent Advances and Applications Vol. 9

Garlic (Allium sativum) derives much of its anticancer properties from sulfur-containing metabolites generated when cloves are crushed, including Allicin and its more stable rearrangement product Z‑Ajoene. Despite its rapid degradation, Allicin induces mitochondrial-driven apoptosis, changes the Nrf2 pathway to alter cellular redox balance, and inhibits drug efflux proteins (such as P glycoprotein) to render chemotherapy-resistant cancer cells more susceptible. Z‑Ajoene has multiple effects, including triggering endoplasmic reticulum stress_(upregulating BiP/GRP78 and activating the PERK/ATF4/CHOP axis blocking Wnt/β_catenin signaling through CK1α-mediated β-catenin phosphorylation, reducing oncogenic drivers like c-Myc, disrupting vimentin filaments to impair invasion, and selectively targeting cancer stem cells through AKT, TGF_β, Notch, and ERK/p38 pathways. Recent translational efforts include nanoformulation of Allicin for better stability and delivery, as well as combination regimens matching these drugs with traditional chemotherapeutics (e.g., 5-FU, paclitaxel), which demonstrate synergistic tumour suppression and lower systemic toxicity. Nanocage-based delivery systems, such as Al₁₂N₁₂ and B₁₂N₁₂, enhance allicin’s stability, bioavailability, and targeted delivery, significantly improving its therapeutic potential.