Volume 3 Supplement 1

Abstracts of the Breast Cancer Immunotherapy Symposium (BRECIS): Sidra Symposia Series

Open Access

Activity of the dietary flavonoid, apigenin, against multidrug-resistant tumor cells as determined by pharmacogenomics and molecular docking

  • Mohamed Saeed1,
  • Thomas Efferth1,
  • Onat Kadioglu1,
  • Hassan Khalid2 and
  • Yoshikazu Sugimoto3
Journal for ImmunoTherapy of Cancer20153(Suppl 1):P10

DOI: 10.1186/2051-1426-3-S1-P10

Published: 14 August 2015

Natural products have been extensively studied and involved in cancer therapy field [1], 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 [2].

Authors’ Affiliations

(1)
Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry - Johannes Gutenberg-University
(2)
Department of Pharmacognosy, University of Khartoum
(3)
Division of Chemotherapy, Faculty of Pharmacy - Keio University

References

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  2. 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

Copyright

© Saeed et al. 2015

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.

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