- Poster presentation
- Open Access
Activity of the dietary flavonoid, apigenin, against multidrug-resistant tumor cells as determined by pharmacogenomics and molecular docking
© Saeed et al. 2015
- Published: 14 August 2015
- Molecular Docking
- mRNA Expression Profile
- Nucleotide Binding Domain
Natural products have been extensively studied and involved in cancer therapy field , apigenin has considerable cytotoxic activity in vitro and in vivo. Despite many mechanistic studies, less is known about resistance factors hampering apigenin’s activity. We investigated the ATP-binding cassette (ABC) transporters BCRP/ABCG2, P-glycoprotein/ABCB1 and its close relative ABCB5. Apigenin inhibited not only P-glycoprotein, but also BCRP by increasing cellular uptake of doxorubicin and showed synergistic inhibitory effect in combination with doxorubicin or docetaxel against multidrug-resistant cells. To perform in silico studies, we first generated homology models for human P-glycoprotein and ABCB5 based on the crystal structure of murine P-glycoprotein. Their nucleotide binding domains (NBDs) revealed the highest degrees of sequence homologies (89%-100%), indicating that ATP binding and cleavage is of crucial importance for ABC transporters. In silico studies showed a pigenin bound to the NBDs of P-glycoprotein and ABCB5. Hence, apigenin may compete with ATP for NBD-binding leading to energy depletion to fuel the transport of ABC transporter substrates. Furthermore, we performed COMPARE and hierarchical cluster analyses of transcriptome-wide mRNA expression profiles of the National Cancer Institute tumor cell line panel. Microarray-based mRNA expressions of genes of diverse biological functions significantly predicted responsiveness of tumor cells to apigenin .
- Newman DJ, Cragg GM: Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod. 2012, 75 (3): 311-35. 10.1021/np200906s.PubMed CentralView ArticlePubMedGoogle Scholar
- Saeed M, Kadioglu O, Khalid H, Sugimoto Y, Efferth T: Activity of the dietary flavonoid, apigenin, against multidrug-resistant tumor cells as determined by pharmacogenomics and molecular docking. J Nutr Biochem. 2015, 26 (1): 44-56. 10.1016/j.jnutbio.2014.09.008.View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.