Publication: Modulation of tamoxifen effects on era-positive and era-negative breast cancer cells by tualang honey
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Date
2014-10
Authors
Said @Fauzi, Agustine Nengsih
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Abstract
Tamoxifen (TAM) is an anti-estrogen drug commonly used for treatment of hormone receptor-positive breast cancer. However, the side effects and cancer cell resistance to TAM limits its clinical efficacy. Therefore, many studies have been conducted to focus on the combination treatment of TAM with new agents or compounds to achieve the treatment objective with minimal side effects. For these reasons and based on the increasing reports of its medicinal use, Tua/ang honey (TH) was selected in this study. The current study aimed to evaluate the role of TH in modulating TAM effects and its death signalling pathways in human breast cancer cells, MCF-7 (ERa-positive) and MDA-MB-231 (ERa-negative) as well as in nonmalignant breast epithelial cells, MCF lOA. Initially, all cells were treated with TH to determine its cytotoxic effects and to identify the type of cell death mechanism. For further analyses, the cells were treated with TH, TAM and the combination of TH+ TAM for determination of apoptotic activity, alteration in mitochondrial membrane potential ('I'm), caspase activation and cell cycle regulation. The effects of TH, TAM and TH+TAM in MCF-7 and MDA-MB-231 cells were also determined at the gene and protein levels by PCR Array system and Western blotting, respectively. The results showed that TH was cytotoxic and induced apoptosis of MCF-7 and MDA-MB-231 cells but not MCFI OA cells. TH modulates TAM activities by promoting late apoptosis and differentially affects TAM-induced cell cycle arrest in MCF-7 and MDA-MB-231 cells. PCR Array data showed remarkable up- and down-regulation of several apoptotic genes in MCF-7 cells including p53 ( ~ 1300-fold), GADD45A ( ~ 120-fold), L TBR ( ~ 790-fold) and BCL-2 ( ~-180-fold), but not in MDA-MB-231 cells. The induction of F ADD, p53 and p21 protein expression in MCF-7 cells showed that TH-induced apoptotic activities are mediated by death receptor and p53-dependent p21 signalling pathways. Increased expression of p21 without elevated level of p53 in MDA-MB-231 cells suggests that the TH induced-apoptotic activity is p53-independent. The ability of TH to modulate TAM apoptotic activities in ERa-positive (MCF-7) and ERa-negative (MDA-MB-231) cells indicates the potential of TH as anticancer agent/adjuvant in breast cancer treatment.
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Keywords
Breast neoplasms