Studies of Anti-Cancer Activity of Folic Acid

We appreciated the grant (2008-2011) sponsored by National Science Council allowing us to conduct the experiments. The research of this project (2008-2011) had been focused on the effect of folic acid in angiogenesis and our results have been published in two papers in Angiogenesis (Lin et al., 2012) and in Biochemical Pharmacology (Hou et al., 2012), respectively. Our data demonstrated that folic acid can inhibit endothelial cell proliferation through activating the cSrc/ERK 2/NF-κB/p53 pathway mediated by folic acid receptor(Lin et al., 2012) and inhibit endothelial cell migration through inhibiting the RhoA activity mediated by activating the folic acid receptor/cSrc/p190RhoGAP-signaling pathway (Hou et al., 2012). Our previous studies also showed that folic acid could inhibit proliferation and migration in COLO-205 cancer cells. The aim of this new grant proposal will be focused on the anti-cancer activity of folic acid. We will extend our previous studies and further investigate in detail how folic acid inhibited the process tumor growth. Clinically, the pregnant women were encouraged to take more folic acid. The results from our previous study suggested that folic acid could induce an anti-angiogenic activity. However, congenital anomaly due to folic acid supplement taken by pregnant women has not been reported. Accordingly, we hypothesize that there are protective mechanisms for pregnant women to escape from the folic acid-induced anti-angiogenesis. Several issues will be addressed in this new proposal study including (1) in vitro and in vivo studies of anti-tumorigenic activity of folic acid; (2) involvement of folic acid receptor in the folic acid-induced anti-tumorigenic activity; and (3) effect of female sex hormones on the folic acid-induced anti-angiogenesis. We will apply the cellular and molecular biology techniques to perform in vitro and in vivo studies in examining the anti-tumorigenesis activity of folic acid and its molecular mechanisms underlying. The outcome of this study will help us getting insight the anti-cancer activity of folic acid and the potential clinical applications of folic acid in cancer therapy