Poster Board Number: A310

Keishla Rodríguez-Mártir (UPR Rio Piedras), Ayeisha Colón-Ortiz (UPR Rio Piedras), Verónica Fuxa-Rey (UPR Rio Piedras), Dalissa Negrón-Figueroa (UPR Rio Piedras), Carlos Morales-Rivera (UPR Rio Piedras), Emmanuel Carrasquillo-Dones (UPR Rio Piedras), Esther Peterson-Peguero (UPR Rio Piedras)

Coumestrol (Cou) is a phytoestrogen present in soy and clover sprouts which is structurally similar to estrogen (E2) and has a cytotoxic effect in breast cancer cell lines. Nevertheless, the molecular mechanism by which Cou can exert its effect in the most aggressive breast cancer subtype, triple-negative inflammatory breast cancer (TN-IBC), is still unknown. Several studies show that TN-IBC cell lines are unresponsive to hormonal therapies, but E2 can activate signaling pathways involved in pro-oncogenic phenotypes such as motility and invasion. Therefore, the objective of this study was to determine if Cou has an anti-cancer effect in TN-IBC cell lines and the molecular mechanism that Cou exerts for its anti-cancer activity using 2D cell culture models. For this, a dose-response curve of Cou in 2D models of TN-IBC cell lines was generated to determine the half-maximal inhibitory concentration (IC50). Also, relative cell viability was performed in ER-positive, triple-negative, TN-IBC, and HER2-amplified IBC cell lines. Functional assays were performed in TN-IBC cell lines to determine the effect of E2 alone, Cou alone, and in a combination of treatments on cell viability, migration, and invasion. Also, the effect on phosphorylation of downstream kinases was analyzed by a proteome profile human phospho-kinase array. An RNA-seq was performed in TN-IBC cell lines to identify transcriptome changes after Cou treatment. Preliminary observations demonstrated that Cou treatment using the IC50 (13µM) caused a decrease in cell viability in TN-IBC cell lines. Similarly, Cou treatment reduces triple-negative non-IBC viability. Also, in comparison with E2, Cou decreases migration and invasion in TN-IBC cell lines. Finally, Cou treatment reduces the phosphorylation of kinases that promote pro-oncogenic phenotypes and upregulate genes involved in breast cancer phenotype suppression. In summary, the data gathered in this study will guide us in elucidating a signaling pathway affected by Cou’s anti-cancer activity. More importantly, it will open the opportunities to design more effective targeted therapeutic strategies to improve the prognosis and survival rates of IBC patients.

Support or Funding Information

This project is supported by NIH R21 (1R21CA253609-01), RISE program (5R25GM061151-20) and UPR Fondos Institucionales para la Investigación (FIPI to E.Peterson).

This project is supported by NIH R21 (1R21CA253609-01), RISE program (5R25GM061151-20) and UPR Fondos Institucionales para la Investigaciamp;oacute;n (FIPI to E.Peterson).