Serum-dependent export of protoporphyrin IX by ATP-binding cassette transporter G2 in T24 cells

Tetsuya Ogino, Hirotsugu Kobuchi, Kazuaki Munetomo, Hirofumi Fujita, Masanao Yamamoto, Toshihiko Utsumi, Keiji Inoue, Taro Shuin, Junzo Sasaki, Masayasu Inoue, Kozo Utsumi

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43 Citations (Scopus)

Abstract

Accumulation of protoporphyrin IX (PpIX) in cancer cells is a basis of 5-aminolevulinic acid (ALA)- induced photodymanic therapy. We studied factors that affect PpIX accumulation in human urothelial carcinoma cell line T24, with particular emphasis on ATP-binding cassette transporter G2 (ABCG2) and serum in the medium. When the medium had no fetal bovine serum (FBS), ALA induced PpIX accumulation in a time- and ALA concentration- dependent manner. Inhibition of heme-synthesizing enzyme, ferrochelatase, by nitric oxide donor (Noc18) or deferoxamine resulted in a substantial increase in the cellular PpIX accumulation, whereas ABCG2 inhibition by fumitremorgin C or verapamil induced a slight PpIX increase. When the medium was added with FBS, cellular accumulation of PpIX stopped at a lower level with an increase of PpIX in the medium, which suggested PpIX efflux. ABCG2 inhibitors restored the cellular PpIX level to that of FBS(-) samples, whereas ferrochelatase inhibitors had little effects. Bovine serum albumin showed similar effects to FBS. Fluorescence microscopic observation revealed that inhibitors of ABC transporter affected the intracellular distribution of PpIX. These results indicated that ABCG2-mediated PpIX efflux was a major factor that prevented PpIX accumulation in cancer cells in the presence of serum. Inhibition of ABCG2 transporter system could be a new target for the improvement of photodynamic therapy.

Original languageEnglish
Pages (from-to)297-307
Number of pages11
JournalMolecular and Cellular Biochemistry
Volume358
Issue number1-2
DOIs
Publication statusPublished - 2011

Keywords

  • 5-Aminolevulinic acid
  • ATP-binding cassette transporter G2
  • Albumin
  • Ferrochelatase
  • Photodynamic therapy
  • Protoporphyrin IX

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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    Ogino, T., Kobuchi, H., Munetomo, K., Fujita, H., Yamamoto, M., Utsumi, T., Inoue, K., Shuin, T., Sasaki, J., Inoue, M., & Utsumi, K. (2011). Serum-dependent export of protoporphyrin IX by ATP-binding cassette transporter G2 in T24 cells. Molecular and Cellular Biochemistry, 358(1-2), 297-307. https://doi.org/10.1007/s11010-011-0980-5