Short chain fatty acids exhibit selective estrogen receptor downregulator (SERD) activity in breast cancer. Academic Article uri icon


  • Early stage estrogen receptor (ER, ESR1)-positive breast cancer patients can develop more aggressive endocrine-resistant tumors that express constitutively active mutant forms of ER including ER-Y537S and ER-D538G. These patients are treated with selective ER down regulators (SERDs) such as the ER antagonist fulvestrant. Previous studies show that histone deacetylase (HDAC) inhibitors downregulate ER and since some dietary derived short chain fatty acids (butyrate, propionate and acetate) exhibit HDAC inhibitory activity we investigated their effects as SERDs in MCF-7 and T47D cells expressing wild-type and mutant ER-D538G and ER-Y537S. The SCFAs exhibited SERD-like activity in both cell lines expressing wild-type and mutant ER. The results for propionate and butyrate correlated with parallel induction of histone acetylation and this was also observed for the HDAC inhibitors Panobinostat, Vorinostat and Entinostat which also downregulated wild-type and mutant ER and induced histone acetylation. Although acetate induced ER degradation the mechanisms may be independent of the HDAC inhibitory activity of this compound. These results suggest that high fibre diets that induce formation of SCFAs may have some clinical efficacy for treating ER-positive endocrine resistant breast cancer patients and this is currently being investigated.

published proceedings

  • Am J Cancer Res

author list (cited authors)

  • Schoeller, A., Karki, K., Jayaraman, A., Chapkin, R. S., & Safe, S.

citation count

  • 2

complete list of authors

  • Schoeller, Abigail||Karki, Keshav||Jayaraman, Arul||Chapkin, Robert S||Safe, Stephen

publication date

  • January 2022