Abstract 5496: Mechanisms of anti-tumurogenic activity of the brown seaweed, F. vesiculosus

Abstract

Abstract Introduction. We previously reported significant anti-estrogenic effects related to the consumption of the brown seaweed, F. vesiculosus. The present study aimed to further characterize the mechanisms involved and to investigate other actions of F. vesiculosus that may be biologically relevant. Methods. Activation of the estrogen receptor was determined using a luciferase reporter assay (CALUX assay) in six breast, ovarian and endometrial cancer cells lines (MCF7, T47D, MDA-MB-231, OVCAR-3 and HEC-1-B) treated with an F. vesiculosus extract. Cell proliferation and apoptosis were determined by the MTT assay and the AnnexinV affinity assay, respectively. Gene expression profiling for 248 genes in pathways including tumor suppression, apoptosis, autophagy, hormonal regulation, cell cycling, proliferation, angiogenesis, inflammation and oxidative stress were analyzed using the nCounter Analysis System (NanoString Technologies, Seattle, WA), and validated by real-time quantitative RT-PCR. A two-way ANOVA model, with cell line effect and treatment dose effect, was fitted to the normalized expression data for each gene. The permutation based F-test was used to identify genes differentially expressed between treatment doses. Results. In co-treatments with 12.5 pM β-estradiol (EC50), F. vesiculosus reduced ER activity by ∼50% at the 1mg/mL dose, showing a potent ER antagonist effect. All cells showed a progressive decrease in proliferation rates, as measured by the MTT assay over 3 days, with increasing concentrations of the seaweed extract, but the sensitivity of individual cell lines was variable. The two endometrial cell lines were most responsive, with up to a 50% reduction in cell number, whereas the MDA-MB-231 breast cancer cell line was least responsive with a 30% overall reduction. Transcription levels of multiple genes were affected by the treatments in all cell lines, with more notable effects in apoptosis, proliferation, and several receptor-mediated signaling pathways. Conclusion. Our results provide new insights into the anti-estrogenic activity of F. vesiculosus through direct inhibition of estrogen receptor activation that may be particularly relevant in the pathogenesis and progression of female cancers. We also found that the F. vesiculosus extract reduced cell proliferation, induced apoptosis and up-regulated genes in signaling pathways that have anti-tumorigenic potential. Citation Format: Jacques E. Riby, Lucia Conde, Xiangqin Cui, Jianqing Zhang, Christine F. Skibola. Mechanisms of anti-tumurogenic activity of the brown seaweed, F. vesiculosus. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5496. doi:10.1158/1538-7445.AM2014-5496