Cancer chemoprevention by phytopolyphenols including flavanoids and flavonoids through modulating signal transduction pathways

Phytopolyphenols are widespread in the plant kingdom and are important in contributing the flavor and color of many fruits and vegetables. They are also important for the normal growth, development, and defense of plants. The important groups of phytopolyphenols in food are flavonoids and flavanoids, which consist mainly of flavones, flavanones, flavonols, flavanonols, isoflavones, flavanols, and anthocyanidines. Although flavanols, also called catechins, seem to be widely distributed in plants, they are rich only in tea leaves, where they may constitute up to 30% of dry leaf weight. The antioxidative, anti-inflammatory, and antitumor properties of green and black teas and their tea polyphenols (flavanoids) are intensively investigated. Recent investigations with phytopolyphenols, including flavanoids (tea catechins, theaflavins, theasinensins, etc.), flavonoids (apigenin, myristin, genistein, etc.), and other polyphenols (curcumin, resveratrol, carnosol, garcinol, etc.), have provided important insights as to how these compounds modulate signal transduction pathways and the role of this modulation in executing their cancer chemopreventive actions. The induction of human cancer involves a multistep process, initiated with DNA damage by endogenous reactive oxygen species (ROS) and exogenous activated carcinogens, followed by oncogene activation and tumor suppressor gene mutations, and finally lead to the alteration of different signaling pathways. Cell cycle arrest, apoptosis, cell proliferation, and cell differentiation are all mediated through signal transduction processes and appeared to be important executive targets for the operation of cancer chemoprevention. Several transducer proteins, such as cdks, cyclins, cdk inhibitors, ROS, cytochrome c, caspases, PARP Bcl-2, Bax, p53, c-jun, c-fos, c-myc, PKC, PKB, PI3K, MAPK, NFkappaB, IKK, etc. are involved in these important cellular functions. Effects of the above mentioned phytopolyphenols on the activities of these transducer proteins were investigated by our laboratory and others, and the results will be selectively described and discussed.