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

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].

References

  1. 1.

    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.

  2. 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.

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Correspondence to Mohamed Saeed.

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Keywords

  • Doxorubicin
  • Docetaxel
  • Molecular Docking
  • mRNA Expression Profile
  • Nucleotide Binding Domain