Anticancer drugs designed by mother nature: ancient drugs but modern targets

Abstract

Nuclear factor-kappaBeta (NF-kappaBeta) is a transcription factor that is activated in response to various inflammatory stimuli such as cytokines, growth factors, hormones, mitogens, carcinogens, chemotherapeutic agents, viral products, eukaryotic parasites, endotoxin, fatty acids, metals, radiation, hypoxia, and psychological, physical, oxidative, and chemical stresses. In addition, constitutively active NF-kappaBeta is frequently encountered in a wide variety of tumors. Furthermore, NF-kappaBeta activation has been shown to regulate the expression of over 400 genes involved in cellular transformation, proliferation, inflammation, viral replication, antiapoptosis, angiogenesis, invasion and metastasis, oxidative stress, and osteoclastogenesis. Therefore, because of the critical role NF-kappaBeta plays in the pathogenesis of cancer, specific inhibitors of this factor are being sought. Agents that prevent cancer or inflammation have been found to suppress NF-kappaBeta activation. Numerous reports indicate that ancient plants and their components are potent as NF-kappaB inibitors. However, ancient medicine such as traditional Chinese medicine, Kampo, Ayurveda requires rediscovery in light of our current knowledge of allopathic (modern) medicine for the therapeutic and preventive purpose. In this review, we present evidence that numerous agents identified from fruits and vegetables can interfere with NF-kappaBeta pathway. The structure of drugs and their relationship with NF-kappaBeta inhibitory activity is discussed.