Folic acid prevents the progesterone-promoted proliferation and migration in breast cancer cell lines

  • Hui-Chen Wang
  • Yen-Nien Huo
  • Wen-Sen LeeEmail author
Original Contribution



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.


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.


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.


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.


Csk cSrc p140Cap p-cSrcY416 p-cSrcY527 



This work was supported by the research grant from the Ministry of Science and Technology, R.O.C. (MOST 107-2320-B-038 -051 -MY3).

Compliance with ethical standards

Conflict of interests

The authors have not conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Graduate Institute of Medical Sciences, College of MedicineTaipei Medical UniversityTaipeiTaiwan
  2. 2.Department of Physiology, School of Medicine, College of MedicineTaipei Medical UniversityTaipeiTaiwan
  3. 3.Cancer Research CenterTaipei Medical University HospitalTaipeiTaiwan
  4. 4.Cell Physiology and Molecular Image Research Center, Wan Fang HospitalTaipei Medical UniversityTaipeiTaiwan

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