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A potential daidzein derivative enhances cytotoxicity of epirubicin on human colon adenocarcinoma Caco-2 cells.
Int J Mol Sci. 2012 Dec 21; 14(1):158-76.IJ

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.

Authors+Show Affiliations

Department of Biological Sciences and Technology, National University of Tainan, Tainan 700, Taiwan. yulilo@mail.nutn.edu.tw.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23344026

Citation

Lo, Yu-Li. "A Potential Daidzein Derivative Enhances Cytotoxicity of Epirubicin On Human Colon Adenocarcinoma Caco-2 Cells." International Journal of Molecular Sciences, vol. 14, no. 1, 2012, pp. 158-76.
Lo YL. A potential daidzein derivative enhances cytotoxicity of epirubicin on human colon adenocarcinoma Caco-2 cells. Int J Mol Sci. 2012;14(1):158-76.
Lo, Y. L. (2012). A potential daidzein derivative enhances cytotoxicity of epirubicin on human colon adenocarcinoma Caco-2 cells. International Journal of Molecular Sciences, 14(1), 158-76. https://doi.org/10.3390/ijms14010158
Lo YL. A Potential Daidzein Derivative Enhances Cytotoxicity of Epirubicin On Human Colon Adenocarcinoma Caco-2 Cells. Int J Mol Sci. 2012 Dec 21;14(1):158-76. PubMed PMID: 23344026.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A potential daidzein derivative enhances cytotoxicity of epirubicin on human colon adenocarcinoma Caco-2 cells. A1 - Lo,Yu-Li, Y1 - 2012/12/21/ PY - 2012/11/09/received PY - 2012/12/12/revised PY - 2012/12/17/accepted PY - 2013/1/25/entrez PY - 2013/1/25/pubmed PY - 2013/1/25/medline SP - 158 EP - 76 JF - International journal of molecular sciences JO - Int J Mol Sci VL - 14 IS - 1 N2 - 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. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/23344026/A_potential_daidzein_derivative_enhances_cytotoxicity_of_epirubicin_on_human_colon_adenocarcinoma_Caco_2_cells_ L2 - https://doi.org/10.3390/ijms14010158 DB - PRIME DP - Unbound Medicine ER -