In addition, polyamines (spermine and spermidine) inhibit the production of tumoricidal cytokines, such as tumor necrosis factor (TNF), and chemokines in vitro, while they do not inhibit production of transforming Akt inhibitor growth factor beta, which has immunosuppressive properties [105–107]. Conversely, in animal experiments, polyamine deprivation has been shown to enhance chemokine production, reverse tumor inoculation-induced inhibition of killer cell activity, and prevent tumor-induced immune suppression [108, 109]. TNF is able to induce apoptotic cell death and to attack and destroy cancer cells

[110], while LFA-1 and CD56, especially bright CD11a and bright CD56 cells, are required for the induction of LAK cell cytotoxic activity [111, 112]. Polyamines suppress LAK cytotoxicity without decreasing cell viability and activity in vitro, and the changes in blood spermine levels are negatively associated with changes in LAK cytotoxicity in cancer patients

[42]. 6. Sources of polyamines other than cancer cells Quizartinib Food is an important source of polyamines. Polyamines in the intestinal lumen are absorbed quickly and distributed to all organs and tissues [29, 39, 40]. Moreover, continuous intake of polyamine-rich food gradually increases blood polyamine levels [30, 31]. Therefore, the restricted intake of food polyamine and inhibition of polyamine synthesis by GW786034 manufacturer microbiota in the intestine with or without inhibitor-induced inhibition of polyamine synthesis is reported to have favorable effects on cancer therapy [33, 113–115]. Trauma, such as surgery, is itself considered to increase the risk

of cancer spread through various mechanisms [116–118]. Blood concentration and urinary excretion of polyamines are known to increase after surgery, although the origin of this increase is not well established [97, 119]. Our previous study showed that increases in blood polyamine levels are inversely associated with anti-tumor LAK cytotoxicities in patients who have undergone surgery [42]. In addition to mechanisms previously postulated for post-traumatic cancer spread, Tenofovir nmr post-operative increases in polyamines may be another factor that accelerates tumor growth. Conclusion As polyamines are essential for cell growth, one of the mechanisms by which polyamines accelerate tumor growth is through the increased availability of this indispensable growth factor. In addition, polyamines seem to accelerate tumor invasion and metastasis not only by suppressing immune system activity against established (already existing) tumors but also by enhancing the ability of invasive and metastatic capability of cancer cells.