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Article

Etoposide increases equilibrative nucleoside transporter 1 activity and fluorothymidine uptake: Screening of 60 cytotoxic agents

  • Authors:
    • Eun Jung Lee
    • Seung Jin Lee
  • View Affiliations / Copyright

    Affiliations: Institute for Innovative Cancer Research, Asan Institute for Life Sciences, Asan Medical Center, Seoul 138-736, Republic of Korea
  • Pages: 763-770
    |
    Published online on: December 10, 2012
       https://doi.org/10.3892/or.2012.2172
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Abstract

Equilibrative nucleoside transporter 1 (ENT1) is a major regulator for the uptake of [18F]fluorothymidine ([18F]FLT), a promising positron emission tomography tracer for treatment monitoring. Various antimetabolites such as 5-fluorouracil often increase ENT1 activity and [18F]FLT uptake (flare) in spite of cell death. However, it has not yet been defined which agents induce [18F]FLT flare and what is the role of [18F]FLT flare in cell viability. Sixty cytotoxic agents from the LOPAC1280 library were screened for ENT1 activity in HeLa cells which predominantly express ENT1, and topoisomerase inhibitors (i.e., aurintricarboxylic acid, idarubicin, camptothecin and etoposide) were identified as potent inducers of ENT1 activity. The changes in ENT1 activity were closely correlated with [3H]FLT uptake (Spearman's correlation coefficient, r=0.66; P<0.01). Etoposide significantly increased ENT1 activity and [3H]FLT uptake accompanying cell cycle arrest at S/G2/M phase and the increase in TK1 expression and activity in both ENT1-low expressing HT29 and ENT1-high expressing MDA-MB-231 cells. The inhibition of ENT1 activity by dipyridamol or S-(p-nitrobenzyl)-6-thioinosine repressed the etoposide-induced cell death in HeLa cells, whereas it induced no changes in the other cell lines. In conclusion, etoposide is identified as a potent inducer for ENT1 activity and [3H]FLT uptake. The role of ENT1 activity by etoposide was cell-type dependent, which requests caution for the application of ENT1-mediated [18F]FLT flare for treatment monitoring.
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Copy and paste a formatted citation
Spandidos Publications style
Lee EJ and Lee SJ: Etoposide increases equilibrative nucleoside transporter 1 activity and fluorothymidine uptake: Screening of 60 cytotoxic agents. Oncol Rep 29: 763-770, 2013.
APA
Lee, E.J., & Lee, S.J. (2013). Etoposide increases equilibrative nucleoside transporter 1 activity and fluorothymidine uptake: Screening of 60 cytotoxic agents. Oncology Reports, 29, 763-770. https://doi.org/10.3892/or.2012.2172
MLA
Lee, E. J., Lee, S. J."Etoposide increases equilibrative nucleoside transporter 1 activity and fluorothymidine uptake: Screening of 60 cytotoxic agents". Oncology Reports 29.2 (2013): 763-770.
Chicago
Lee, E. J., Lee, S. J."Etoposide increases equilibrative nucleoside transporter 1 activity and fluorothymidine uptake: Screening of 60 cytotoxic agents". Oncology Reports 29, no. 2 (2013): 763-770. https://doi.org/10.3892/or.2012.2172
Copy and paste a formatted citation
x
Spandidos Publications style
Lee EJ and Lee SJ: Etoposide increases equilibrative nucleoside transporter 1 activity and fluorothymidine uptake: Screening of 60 cytotoxic agents. Oncol Rep 29: 763-770, 2013.
APA
Lee, E.J., & Lee, S.J. (2013). Etoposide increases equilibrative nucleoside transporter 1 activity and fluorothymidine uptake: Screening of 60 cytotoxic agents. Oncology Reports, 29, 763-770. https://doi.org/10.3892/or.2012.2172
MLA
Lee, E. J., Lee, S. J."Etoposide increases equilibrative nucleoside transporter 1 activity and fluorothymidine uptake: Screening of 60 cytotoxic agents". Oncology Reports 29.2 (2013): 763-770.
Chicago
Lee, E. J., Lee, S. J."Etoposide increases equilibrative nucleoside transporter 1 activity and fluorothymidine uptake: Screening of 60 cytotoxic agents". Oncology Reports 29, no. 2 (2013): 763-770. https://doi.org/10.3892/or.2012.2172
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