Nimbolide as a multi-targeted phytochemical against prostate cancer therapy: Current evidence and future directions

Prostate cancer remains one of the leading causes of cancer-related morbidity and mortality among men worldwide. Despite considerable progress in early detection and androgen receptor-targeted therapies, the management of advanced and castration-resistant prostate cancer continues to present major clinical challenges. Nimbolide, a bioactive limonoid derived from Azadirachta indica (neem), has emerged as a promising natural compound with potent anticancer potential. This phytochemical exerts pleiotropic effects on multiple cellular processes, including proliferation, apoptosis, migration, invasion, angiogenesis, and oxidative stress. Mechanistically, nimbolide regulates both intrinsic and extrinsic apoptotic pathways through modulation of PI3K/Akt/mTOR, STAT3, NF-κB, and Bcl-2 signaling. It further inhibits metastasis and angiogenesis via HDAC6 inhibition and stabilization of cytoskeletal dynamics. In vivo studies using xenograft and transgenic mouse models confirm its ability to suppress tumor growth and metastasis with minimal systemic toxicity. This review summarizes the recent in vitro and in vivo evidence supporting nimbolide's anticancer potential in prostate cancer and discusses its molecular targets, pharmacokinetic limitations, and translational prospects.