**4. Conclusion**

A striking global research on substances derived from natural products including polyphenolic compounds is being explored to understand the detailed mechanisms of their chemopreventive, antitumoral and chemosensibilizing activities against various types of aggressive and recurrent cancers. Besides the involvement of altered redox status in apoptosis induction triggered by these compounds, anti-inflammatory effects, antiangiogenesis, anti-invasiveness and induction of differentiation are well known to be implicated in their broad biological functions. It is worthy of note that flavonoids have been revealed to inhibit the function of ATP-binding cassette transporters such as multidrug resistance-associated proteins as well as P-glycoprotein [90], similar to our recent study [91]. On the other hand, a recent study demonstrated that berry anthocyanins, such as cyanidin-3-galactosidee, and cyanidin-3-glucoside as well as peonidin-3-glucosid, exhibit affinities for the efflux transporters breast cancer resistance protein (BCRP) and consequently may be actively transported out of intestinal tissues and endothelia [92]. However, the same report also demonstrated that some berry anthocyanins and anthocyanidins, such as delphinidin, cyanidin and cyanidin-3-rutinoside, act as BCRP inhibitor, while some of them, such as malvidin, malvidin-3-galactoside and petunidin, exhibited bimodal activities serving as BCRP substrates and inhibitors at low concentrations and high concentrations, respectively [92]. These findings suggest that a variety of biological activities of anthocyanins and anthocyanidins may be attributed in part to their inhibitory effects on those drug transporters, paradoxically, may be abolished as a result of efflux through those transporters. These findings also raised a pharmacological and pharmaceutical concern about formulatability of the dietary constituent, and warn us against the casual use of herbs and/or other botanicals in cancer patient care.
