Natural polyphenols that display anticancer properties through inhibition of kinase activity.

Over eleven hundred publications reporting anticancer activities of polyphenols have appeared in the peer-reviewed literature. In addition, a search of the PubMed database using "polyphenols - cancer - review" as keywords produced over 320 hits for review articles (July 2009). Polyphenol anticancer activities include, among others, anti-oxidative, pro-apoptotic, DNA damaging, anti-angiogenic, and immunostimulatory effects. Targeting specific protein kinases to combat cancer represents a major focus of oncology research within the so-called targeted therapy approach. An exhaustive search of the PubMed database (July 2009) using "polyphenols - cancer - kinases" as keywords resulted in more than 130 hits, half of them having been published within the past five years. Furthermore, the PubMed database contains 25 reviews on the subject of anti-kinase activity of some specific polyphenols, including mainly curcumin and the green tea polyphenol (-)-epigallocatechin 3-gallate (EGCG). However, no attempt has been made yet to review this area of research in a comprehensive, general manner. The current review therefore aims to highlight those anticancer polyphenols that target specific kinases in various types of cancer. The present review also provides an in-depth analysis of polyphenol structure- activity relationships in relation to their anticancer activities and specific kinase targeting. Lastly, a number of polyphenols are identified as potential antitumor agents that could be used to combat biologically aggressive cancers, including metastasizing cancers, through the targeting of specific kinases.