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 language | English |
|---|---|
| Pages (from-to) | 297-307 |
| Number of pages | 11 |
| Journal | Molecular and Cellular Biochemistry |
| Volume | 358 |
| Issue number | 1-2 |
| DOIs | |
| Publication status | Published - 2011 |
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Keywords
- 5-Aminolevulinic acid
- Albumin
- ATP-binding cassette transporter G2
- Ferrochelatase
- Photodynamic therapy
- Protoporphyrin IX
ASJC Scopus subject areas
- Clinical Biochemistry
- Molecular Biology
- Cell Biology
Cite this
Serum-dependent export of protoporphyrin IX by ATP-binding cassette transporter G2 in T24 cells. / Ogino, Tetsuya; Kobuchi, Hirotsugu; Munetomo, Kazuaki; Fujita, Hirofumi; Yamamoto, Masanao; Utsumi, Toshihiko; Inoue, Keiji; Shuin, Taro; Sasaki, Junzo; Inoue, Masayasu; Utsumi, Kozo.
In: Molecular and Cellular Biochemistry, Vol. 358, No. 1-2, 2011, p. 297-307.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Serum-dependent export of protoporphyrin IX by ATP-binding cassette transporter G2 in T24 cells
AU - Ogino, Tetsuya
AU - Kobuchi, Hirotsugu
AU - Munetomo, Kazuaki
AU - Fujita, Hirofumi
AU - Yamamoto, Masanao
AU - Utsumi, Toshihiko
AU - Inoue, Keiji
AU - Shuin, Taro
AU - Sasaki, Junzo
AU - Inoue, Masayasu
AU - Utsumi, Kozo
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
KW - 5-Aminolevulinic acid
KW - Albumin
KW - ATP-binding cassette transporter G2
KW - Ferrochelatase
KW - Photodynamic therapy
KW - Protoporphyrin IX
UR - http://www.scopus.com/inward/record.url?scp=84857183545&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84857183545&partnerID=8YFLogxK
U2 - 10.1007/s11010-011-0980-5
DO - 10.1007/s11010-011-0980-5
M3 - Article
C2 - 21748335
AN - SCOPUS:84857183545
VL - 358
SP - 297
EP - 307
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
SN - 0300-8177
IS - 1-2
ER -