Neem Limonoids as Anticancer Agents: Modulation of Cancer Hallmarks and Oncogenic Signaling

Neem (Azadirachta indica A. Juss) is one of the most versatile medicinal plants, widely distributed in the Indian subcontinent. Neem is a rich source of limonoids that are endowed with potent medicinal properties predominantly antioxidant, anti-inflammatory, and anticancer activities. Azadirachtin, gedunin, and nimbolide are more extensively investigated relative to other neem limonoids. Accumulating evidence indicates that the anticancer effects of neem limonoids are mediated through the inhibition of hallmark capabilities of cancer such as cell proliferation, apoptosis evasion, inflammation, invasion, and angiogenesis. The neem limonoids have been demonstrated to target oncogenic signaling kinases and transcription factors chiefly, NF-κB, Wnt/β-catenin, PI3K/Akt, MAPK, and JAK/STAT signaling pathways. Neem limonoids that target multiple pathways that are aberrant in cancer are ideal candidates for cancer chemoprevention and therapy.