A Potential Daidzein Derivative Enhances Cytotoxicity of Epirubicin on Human Colon Adenocarcinoma Caco-2 CellsReport as inadecuate




A Potential Daidzein Derivative Enhances Cytotoxicity of Epirubicin on Human Colon Adenocarcinoma Caco-2 Cells - Download this document for free, or read online. Document in PDF available to download.

Department of Biological Sciences and Technology, National University of Tainan, Tainan 700, Taiwan





Abstract In this study, we evaluated the effects of 8-hydroxydaidzein 8HD, an isoflavone isolated from fermented soy germ koji, and epirubicin Epi, an antineoplastic agent, on the production of reactive oxygen species ROS. We subsequently correlated the ROS levels to the anticancer mechanisms of Epi and 8HD in human colon adenocarcinoma Caco-2 cells. 8HD enhanced cytotoxicity of Epi and generated a synergistic effect. Epi and-or 8HD treatments increased the hydrogen peroxide and superoxide levels. Combined treatment markedly decreased mRNA expression levels of multidrug resistance protein 1 MDR1, MDR-associated protein MRP 1, and MRP2. 8HD significantly intensified Epi intracellular accumulation in Caco-2 cells. 8HD and-or Epi-induced apoptosis, as indicated by the reduced mitochondrial membrane potential and increased sub-G1 phase in cell cycle. Moreover, 8HD and Epi significantly enhanced the mRNA expressions of Bax, p53, caspases-3 -8, and -9. To our best knowledge, this study verifies for the first time that 8HD effectively circumvents MDR in Caco-2 cells through the ROS-dependent inhibition of efflux transporters and p53-mediated activation of both death receptor and mitochondrial pathways of apoptosis. Our findings of 8HD shed light on the future search for potential biotransformed isoflavones to intensify the cytotoxicity of anticancer drugs through simultaneous reversal of pump and nonpump resistance. View Full-Text

Keywords: multidrug resistance; reactive oxygen species; apoptosis; epirubicin; 8-hydroxydaidzein; isoflavones multidrug resistance; reactive oxygen species; apoptosis; epirubicin; 8-hydroxydaidzein; isoflavones





Author: Yu-Li Lo

Source: http://mdpi.com/



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