P123 Additive antitumor effect of plant polyphenols and a synthetic inhibitors of polyamines biosynthesis

others. Tea is among the most highly consumed beverages worldwide. Derived from the plant Camellia sinensis, tea is consumed in different parts of the world as green, black, or oolong tea. Green tea is favored in Japan and China, and it contains characteristic polyphenolic compounds including (−)-epigallocatechin-3-gallate (EGCG), (−)-epigallocatechin (EGC), (−)-epicatechin-3-gallate (ECG), (−)-epicatechin (EC), (+)-gallocatechin (GC), and (+)-catechin (C). To date, tea catechins have attracted considerable interest due to the potentially health-promoting properties of these substances, including strong antioxidant activity and cancer chemopreventive effects [3, 4]. In a lot of in vitro studies, plant polyphenols were found to suppress proliferation of human and animal malignant cells, especially lung, intestinal, prostate tumors, hepatoma, leukemia and others [5, 6]. Antitumor and antimetastatic activities of plant polyphenols were also shown in the in vivo experiments and were confirmed in extended epidemiological studies demonstrating the lowest levels of breast and prostate cancer morbidity in the countries where green tea and soybean foods consumption is widespread and regular. The exact mechanisms of action of green tea polyphenols remain obscure, but it is known that plant polyphenols possess antioxidative capacity derived from their ability to scavenge reactive oxygen species and trap hydroxyl and peroxyl radicals and inhibits angiogenesis. The well-described antioxidant properties of tea catechins [7] may contribute to the antiproliferative and proapoptotic capacity of green tea by inhibiting NF-kB activity [8, 9]. Recent works demonstrated that polyphenols cause inhibition of polyamine (PA) synthesis in tumor cells. PA — spermine, spermidine and putrescine are known as obligate agents for proliferation of any cells including malignant ones. It is necessary to point that PA per se and enzymes involved in their metabolism are regarded now as available targets for antitumor treatment. Inhibition of PA synthesis in tumor cells was shown to retard their proliferation and tumor growth. A lot of foreign publications as well as our own works show an essential growth retardation of different kinds of experimental tumors via inhibition of PA synthesis. This effect was recently demonstrated in clinical trials, especially, the data on α-DFMO application to prevention and therapy of intestinal cancer [10]. Our previous studies showed that the influence of PA on the functioning of the NF-kВ nuclear transcription factor may be an important way to control tumor growth. We have shown that PA, especially spermine, have specific affinity for the p50 subunit of NF-kВ and