ANTICANCERACTIVITYOFDRUGSFROM AZADIRACHTA INDICA [NEEM] PLANT

Abstract

Azadirachta indica (Neem), a cornerstone of traditional Indian medicine, has emerged as a promising source of anticancer agents due to its rich repertoire of bioactive limonoids, including nimbolide, azadirachtin, and gedunin. These compounds exhibit potent cytotoxic, antiproliferative, anti-angiogenic, and anti-metastatic effects across diverse cancer models. Nimbolide, the most extensively studied neem constituent, induces apoptosis through both intrinsic and extrinsic pathways, modulates Bcl-2 family proteins, and causes cell-cycle arrest by regulating cyclins and cyclin-dependent kinases (CDKs). Neem limonoids suppress angiogenesis by inhibiting VEGF- and IGF-1R-mediated PI3K/Akt/HIF-1α signaling, while also reducing metastatic potential through the downregulation of matrix metalloproteinases and epithelial-to-mesenchymal transition markers. Gedunin disrupts Hsp90 chaperone function, destabilizing oncogenic proteins and triggering endoplasmic reticulum stress. Neem extracts further enhance antitumor immunity by promoting dendritic cell maturation, boosting CD8+ T-cell responses, and inhibiting immunosuppressive cells such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Additionally, neem demonstrates chemopreventive effects by elevating antioxidant defenses and activating detoxification enzymes. Despite compelling preclinical evidence, translational progress is hindered by poor solubility, limited bioavailability, and insufficient clinical data. Therefore, standardized formulations and rigorous clinical trials are essential to validate neem-derived compounds as effective anticancer therapeutics.