Author Kobuchi, Hirotsugu| Moriya, Koko| Ogino, Tetsuya| Fujita, Hirofumi| Inoue, Keiji| Shuin, Taro| Yasuda, Tatsuji| Utsumi, Kozo| Utsumi, Toshihiko|
Published Date 2012-11-26
Publication Title PLoS ONE
Volume volume7
Issue issue11
Content Type Journal Article
JaLCDOI 10.18926/AMO/50408
FullText URL 67_3_153.pdf
Author Yamamoto, Masanao| Fujita, Hirofumi| Katase, Naoki| Inoue, Keiji| Nagatsuka, Hitoshi| Utsumi, Kozo| Sasaki, Junzo| Ohuchi, Hideyo|
Abstract Ever since protoporphyrin IX (PpIX) was discovered to accumulate preferentially in cancer cells after 5-aminolevulinic acid (ALA) treatment, photodynamic treatment or therapy (PDT) has been developed as an exciting new treatment option for cancer patients. However, the level of PpIX accumulation in oral cancer is fairly low and insufficient for PDT. Ferrochelatase (FECH) and ATP-binding cassette transporter G2 (ABCG2) are known to regulate PpIX accumulation. In addition, serum enhances PpIX export by ABCG2. We investigated here whether and how inhibitors of FECH and ABCG2 and their combination could improve PpIX accumulation and PDT efficacy in an oral cancer cell line in serum-containing medium. ABCG2 inhibitor and the combination of ABCG2 and FECH inhibitors increased PpIX in the presence of fetal bovine serum (FBS) in an oral cancer cell line. Analysis of ABCG2 gene silencing also revealed the involvement of ABCG2 in the regulation of PpIX accumulation. Inhibitors of FECH and ABCG2, and their combination increased the efficiency of ALA-PDT even in the presence of FBS. ALA-PDT-induced cell death was accompanied by apoptotic events and lipid peroxidation. These results suggest that accumulation of PpIX is determined by the activities of ABCG2 and FECH and that treatment with a combination of their inhibitors improves the efficacy of PDT for oral cancer, especially in the presence of serum.
Keywords 5-aminolevulinic acid protoporphyrin IX oncology photodynamic therapy apoptosis
Amo Type Original Article
Published Date 2013-06
Publication Title Acta Medica Okayama
Volume volume67
Issue issue3
Publisher Okayama University Medical School
Start Page 153
End Page 164
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
Copyright Holders CopyrightⒸ 2013 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 23804138
Web of Science KeyUT 000320747900004
Related Url
Author Fujita, Hirofumi| Shiosaka, Masahiko| Ogino, Tetsuya| Okimura, Yuya| Utsumi, Toshihiko| Sato, Eisuke F.| Akagi, Reiko| Inoue, Masayasu| Utsumi, Kozo| Sasaki, Junzo|
Published Date 2008-06-23
Publication Title Brain Research
Volume volume1206
Content Type Journal Article