Hemoglobin-fructose glycation products attenuate tamoxifen induced loss of viability in MCF-7 breast cancer cells.

Advanced Glycation End Products (AGEs) form as a result of non-enzymatic addition of reducing sugars to proteins, producing a chemically heterogeneous set of compounds with altered physicochemical properties. Generally, AGEs are considered pro-cancerous in nature due to their reactivity with extracellular, intracellular and membranous components of the cancerous-tissue microenvironment. Despite many studies on AGE-Cancer association, direct evidence linking glycation product preparations to endocrine therapy remains limited. In this study, Hemoglobin Advanced Glycation End Products (Hb-AGEs) have been generated in-vitro by incubating a mixture of hemoglobin and fructose at physiological (37 °C) and accelerated (60 °C) conditions. The end products have been characterized by biophysical and biochemical techniques followed by a functional testing in MCF-7 breast cancer cells. We show that the Hb-AGEs formed in our study contain reducing and radical scavenging (antioxidant) properties which are enhanced under accelerated (at 60 °C) conditions. Functionally, co-treatment of MCF-7 breast cancer cells with Hb-AGEs and tamoxifen protected the cells from tamoxifen toxicity. Given the chemical complexity of the reaction products and lack of mechanistic cellular assays, the observed modulation in tamoxifen response may reflect multiple non-exclusive mechanisms. Rather than simple antioxidant neutralization of the drug-response, these mechanisms may also include altered drug bioavailability, cell-membrane related changes and other downstream stress pathways. Nevertheless, our findings from this study provide a preliminary biochemical and functional framework to further investigate how glycation products may influence chemotherapeutic response in-vitro.