Abstract
BackgroundWe previously reported the anti-estrogenic activity of the brown seaweed, Fucus vesiculosus. The present study aimed to further investigate its anti-estrogenic modes of action and to assess other potentially biologically relevant anti-tumorigenic effects in estrogen receptor (ER)-dependent and -independent female cancer cell lines.MethodsThe CALUX® assay was used to determine the effect of a F. vesiculosus extract (FVE) on activation of the ER. Aromatase enzymatic activity was measured to determine the potential effect of FVE on estradiol (E2) biosynthesis. Transcriptional activity profiling of 248 genes involved in cancer, immunity, hormonal regulation, protein phosphorylation, transcription, metabolism, and cellular structure was conducted using the NanoString nCounter® analysis system in FVE-treated breast, ovarian and endometrial cancer cell lines. The effects of FVE on cell viability, morphology, membrane integrity, mitochondrial toxicity, induction of apoptotic and autophagic markers, and cell signaling were also analyzed.ResultsIn co-treatments with 12.5 pM (EC50) E2, FVE (2 %) reduced ER activation by 50 %, exhibiting potent ER antagonistic effects. FVE inhibited aromatase activity in an in vitro assay (IC50 2.0 %). ER-dependent and -independent cancer cell lines showed significantly decreased viability that correlated with increasing FVE concentrations and altered morphological features suggestive of apoptosis and autophagy. Expression of genes that were significantly altered by FVE (p < 0.05) revealed predominantly apoptotic, autophagic and kinase signaling pathways. FVE also effectively inhibited the phosphorylation of Akt, resulting in reduced mTORC1 activities to stimulate autophagy in cells. Concentration-dependent cleavage of PARP and induction of caspase-3 and -7 activities were observed in MDA-MB-231 cells supporting a role for FVE in the promotion of apoptosis.ConclusionsOur study provides new insights into the anti-estrogenic activity of F. vesiculosus. Moreover, the induction of autophagy and apoptosis on breast, endometrial and ovarian cancer cell lines suggests additional anti-tumorigenic actions of FVE that are independent of ER status in female cancers.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-016-1129-6) contains supplementary material, which is available to authorized users.
Highlights
We previously reported the anti-estrogenic activity of the brown seaweed, Fucus vesiculosus
Anti-estrogenic action was further demonstrated where dosing with a F. vesiculosus extract (FVE) in primary human luteinized granulosa cell cultures led to marked reductions in E2 levels [2]
FVE inhibits estrogen receptor (ER) activation and aromatase activity We previously reported the anti-estrogenic activity of F. vesiculosus, and that one mode of action was competitive inhibition of E2 binding to the ER [1, 2]
Summary
We previously reported the anti-estrogenic activity of the brown seaweed, Fucus vesiculosus. The present study aimed to further investigate its anti-estrogenic modes of action and to assess other potentially biologically relevant anti-tumorigenic effects in estrogen receptor (ER)-dependent and -independent female cancer cell lines. Brown seaweeds such as Fucus vesiculosus are widely consumed by the public due to their potential anti-cancer activities warranting the need for further studies to characterize their biological actions. Anti-estrogenic action was further demonstrated where dosing with a F. vesiculosus extract (FVE) in primary human luteinized granulosa cell cultures led to marked reductions in E2 levels [2]. FVE exerted inhibitory effects on the binding of E2 to estrogen receptor (ER)α and ERβ [2]
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