ALOE EMODIN ENHANCES TAMOXIFEN CYTOTOXICITY EFFECT ON ERa-POSITIVE BREAST CANCER CELLS, MCF-7, THROUGH DOWNREGULATION OF MEK1 AND MEK2

The positive response to tamoxifen in ERa-positive breast cancer patients is usually of a short duration as manyof the patients eventually develop resistance. Our preliminary results show that aloe emodin extracted fromthe leaves of the Aloe barbadensis Miller demonstrated a cytotoxicity that is selective to ERa-positive breastcancer 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 ofMCF-7 cells to treatment with tamoxifen. MCF-7 cells were treated with aloe emodin alone, tamoxifen aloneor a combination of emodin and tamoxifen, at their respective IC50 concentrations and at different time pointsof 24 hours, 48 hours and 72 hours. The respective IC50s were the concentrations of aloe emodin and tamoxifenrequired to achieve 50% inhibition of the cells in the study. Cell viability and apoptosis were determined usingtrypan blue exclusion and DNA fragmentation assays, respectively. The involvement of RAS/MEKs/ERKs genesof MAPK signalling pathways with aloe emodin was determined using QuantiGene 2.0 Plex assay. Data wasevaluated using the one-way ANOVA test. Our findings showed that aloe emodin enhanced the cytotoxicity oftamoxifen on MCF-7 cells through apoptosis by downregulation of MEK1/2 genes. Our research may provide arational basis for further in vivo studies to verify the efficacy of a combination of aloe emodin and tamoxifenon the viability of ERa-positive-breast cancer cells.