{Reference Type}: Journal Article
{Title}: Folic acid prevents the progesterone-promoted proliferation and migration in breast cancer cell lines.
{Author}: Wang HC;Huo YN;Lee WS;
{Journal}: Eur J Nutr
{Volume}: 59
{Issue}: 6
{Year}: Sep 2020
{Factor}: 4.865
{DOI}: 10.1007/s00394-019-02077-3
{Abstract}: <B>OBJECTIVE: </B>We previously demonstrated that progesterone (P4) interacted with folic acid (FA) and abolished the FA-reduced endothelial cell proliferation and migration. These findings led us to investigate whether FA can interfere with the P4-promoted breast cancer cell proliferation and migration.<BR><B>METHODS: </B>We conducted MTT and wound healing assay to evaluate cell proliferation and migration, respectively. Western blot analysis and immunoprecipitation were performed to examine the protein expression and protein-protein interaction, respectively.<BR><B>RESULTS: </B>We demonstrated that P4 promoted proliferation and migration of breast cancer cell lines (T47D, MCF-7, BT474, and BT483). However, co-treatment with P4 and FA together abolished these promotion effects. Treatment with P4 alone increased the formation of PR-cSrc complex and the phosphorylation of cSrc at tyrosine 416 (Tyr416). However, co-treatment with P4 and FA together increased the formations of cSrc-p140Cap, cSrc-Csk, and cSrc-p-Csk complex, and the phosphorylation of cSrc at tyrosine 527 (Tyr527). Co-treatment with P4 and FA together also abolished the activation of cSrc-mediated signaling pathways involved in the P4-promoted breast cancer cell proliferation and migration.<BR><B>CONCLUSIONS: </B>Co-treatment with FA and P4 together abolished the P4-promoted breast cancer cell proliferation and migration through decreasing the formation of PR-cSrc complex and increasing the formations of cSrc-p140Cap and cSrc-Csk complex, subsequently activating Csk, which in turn suppressed the phosphorylation of cSrc at Tyr416 and increased the phosphorylation of cSrc at Tyr527, hence inactivating the cSrc-mediated signaling pathways. The findings from this study might provide a new strategy for preventing the P4-promoted breast cancer progress.