Prospects for Plant-Derived Chemopreventive Agents Exhibiting Multiple Mechanisms of Action
L. M. Howells,
M. M. Manson.
There is great potential for the use of plant-derived agents in the fight to prevent onset or delay progression of the carcinogenic process. Epidemiological evidence for their chemopreventive action is compelling, but even though many of these compounds have an extensive history of use within the human populace, it is of increasing importance to determine more precisely the primary targets contributing to their efficacy, prior to embarking on large-scale clinical trials. This rapidly moving field now concentrates in particular, on the modulating effects these agents can have on cellular signalling pathways involved in the apoptotic, proliferative and angiogenic processes, perturbances to which, are common in many cancers. It is perhaps the ability of these agents to exhibit multi-site mechanisms of action that offers their key to success where conventional single-site agents have disappointed in the past. As well as being promising chemopreventive agents, there is also an exciting role for these compounds in combinatorial therapy with more traditional chemotherapeutics, potentially in lowering of toxicity and enhancing efficacy for treatment of more advanced cancers. This review will summarise known and proposed mechanisms of action for various chemopreventive agents of interest highlighting their potential in combination therapy, and will address benefits and problems of using such multi-site agents in long-term prevention/therapeutic regimes.
Keywords: chemoprevention, cell signalling, combination therapy, indole-carbinol, curcumin, epigallocatechin gallate, resveratrol
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