Improvement of the efcacy of 5-aminolevulinic acid-mediated photodynamic treatment in human oral squamous cell carcinoma hsc-4

Masanao Yamamotoarf, Hirofumi Fujitaa, Naoki Katase, Keiji Inouec, Hitoshi Nagatsuka, Kozo Utsumi, Junzo Sasaki, Hideyo Ohuchi

Research output: Contribution to journalArticle

14 Citations (Scopus)

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 fine 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 fine. 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 pres¬ence of FBS. ALA-PDT-induced cell death was accompanied by apoptotic events and lipid peroxida-tion. 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

Original languageEnglish
Pages (from-to)153-164
Number of pages12
JournalActa medica Okayama
Volume67
Issue number3
Publication statusPublished - Sep 3 2013

Keywords

  • 5-aminolevulinic acid
  • Apoptosis
  • Oncology
  • Photodynamic therapy
  • Protoporphyrin IX

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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