Bile acids (BA) are classically known as an agent important in lipid absorption and cholesterol metabolism. Nowadays, BAs have been found to be involved in various cellular signaling pathways such as protein kinase cascades, cyclic AMP (cAMP) synthesis and calcium mobilization. In addition, they have also been shown to regulate glucose and energy homeostasis. Bile acids are ligands for several nuclear hormone receptors, including FXR. Recently, muscarinic receptor and TGR5, G-protein-coupled receptor (GPCR), have been suggested to play a role in bile acid activity which is independent of nuclear hormone receptors. Moreover, BAs have also been studied in other GPCR associated pathways, namely sphingosine-1-posphate and glucagon receptor. Hydrophobic bile acids have been proven to affect heart rate and its contraction. Elevated bile acids are associated with arrhythmias in adults and fetal heart. Altered ratios of primary and secondary bile acid are reported in chronic heart failure patients. Meanwhile in patients with liver cirrhosis, cardiac dysfunction has been strongly linked to the increase of serum bile acid concentrations. In contrast, the most hydrophilic BA known as ursodeoxycholic acid has been found beneficial in improving peripheral blood flow in chronic heart failure patients and protecting heart against reperfusion injury.

The positive response to tamoxifen in ERa-positive breast cancer patients is usually of a short duration as many of the patients eventually develop resistance. Our preliminary results show that aloe emodin extracted from the leaves of the Aloe barbadensis Miller demonstrated a cytotoxicity that is selective to ERa-positive breast cancer cells (MCF-7), but not to ERa-negative breast cancer cells (MDA-MB-231) and to the control cells (MCF-10A). The objective of this study was to test the hypothesis that aloe emodin may enhance the response of MCF-7 cells to treatment with tamoxifen. MCF-7 cells were treated with aloe emodin alone, tamoxifen alone or a combination of emodin and tamoxifen, at their respective IC 50 concentrations and at different time points of 24 hours, 48 hours and 72 hours. The respective IC 50s were the concentrations of aloe emodin and tamoxifen required to achieve 50% inhibition of the cells in the study. Cell viability and apoptosis were determined using trypan blue exclusion and DNA fragmentation assays, respectively. The involvement of RAS/MEKs/ERKs genes of MAPK signalling pathways with aloe emodin was determined using QuantiGene 2.0 Plex assay. Data was evaluated using the one-way ANOVA test. Our findings showed that aloe emodin enhanced the cytotoxicity of tamoxifen on MCF-7 cells through apoptosis by downregulation of MEK1/2 genes. Our research may provide a rational basis for further in vivo studies to verify the efficacy of a combination of aloe emodin and tamoxifen on the viability of ERa-positive-breast cancer cells.