Interactions between Female Sex Hormones and Folic Acid

Under the grant support (2013-2014) by National Science Council, we have finished the investigation of the molecular mechanisms underlying folic acid (FA)-induced anti-proliferation in COLO-205 and the in vivo study of FA in the COLO-205 tumor growth. Our results demonstrated that FA can activate the FRα/cSrc/ERK1/2/NFκB/p53-mediated signaling pathway, which in turn increase the expression of p21 and p27 protein, and finally cause proliferation inhibition in cultured COLO-205. The results from our in vivo studies demonstrated that FA (100 and 300 μg) can increase the levels of p21, p21 and p53 protein in the COLO-205 tumor, profound reduce the tumor volume and prolong the life span of COLO-205 bearing mice. These results have been submitted for publication [Kuo et al., submitted for publication]. Our preliminary studies also found that female sex hormones (estrogen and progesterone) can prevent the FA-induced anti-proliferation and anti-migration in endothelial cells and COLO-205. These findings led us to hypothesize that FA and female sex hormones can interfere with each other on the biological activities We will use three models to examine our hypothesis including (1) effect of female sex hormones on the FA-induced anti-angiogenesis; (2) effect of female sex hormones on the FA-induced anti-cancer activity; and (3) effect of FA on female sex hormones-induced enhancement on breast cancer cell migration. The molecular mechanisms underlying interactions between FA and female sex hormones will be also investigated. The siRNA techniques will be applied to examine the role of FA receptor, estrogen receptor, progesterone receptor and some other molecules involved in the signaling pathways in the interactions between FA and estrogen or progesterone. The outcome of this study will help us getting insight how female sex hormones might affect the biologic actions and the potential clinical applications of FA.