title: Concomitant treatment with temozolomide enhances apoptotic cell death in glioma cells induced by photodynamic therapy with talaporfin sodium.
abstract: BACKGROUND
  Photodynamic therapy (PDT) induces selective cell death of neoplastic tissue and connecting vasculature by combining photosensitizers with light. We have previously reported that PDT induces apoptotic cell death in glioma cells when the photosensitizer talaporfin sodium (NPe6) is used. Here, we investigated the combined effect of NPe6-PDT with temozolomide, a DNA-alkylating drug used in glioma therapy.
  
  
  METHODS
  Human glioblastoma T98G cells and human glioma U251 cells were used as glioma cells. Cell viability was evaluated by WST-8 assay. Apoptosis was evaluated by measurement of caspase-3 activity and DNA-fragmentation. Intracellular reactive oxygen species were evaluated by dihydrorhodamine assay.
  
  
  RESULTS
  While the degree of NPe6-PDT induced cell death unchanged in T98G and U251 cells when temozolomide treatment was adjuvant, it was dose-dependently increased by concomitant treatment with temozolomide. Further, concomitantly administered temozolomide dose-dependently increased caspase-3 activity and DNA-fragmentation, while adjuvant-temozolomide did not. These results are suggesting that concomitantly administered temozolomide potentiates the effect of NPe6-PDT to facilitate apoptotic cell death. Additionally, concomitantly administered temozolomide increased intracellular NPe6-fluorescence and reactive oxygen species, suggesting that the augmentation effect of combined treatment may be due to increased intracellular accumulation of NPe6.
  
  
  CONCLUSIONS
  These results suggest that concomitant treatment with NPe6-PDT and temozolomide is a potentially useful therapy for glioma.
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. Electronic address: miki@ps.toyaku.ac.jp.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Miki
authors.affiliation: Department of Neurosurgery, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku, Tokyo 160-0023, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Akimoto
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Omata
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Moritake
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Michika
authors.initials: M
authors.lastname: Hiranuma
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Hironaka
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Beppu
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004359:Drug Therapy, Combination; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage; D011166:Porphyrins / Q000008:administration & dosage*; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D017319:Photosensitizing Agents; D011166:Porphyrins; D003606:Dacarbazine; C053434:Talaporfin; D000077204:Temozolomide
keywords: Apoptosis; Glioma; Mono-L-aspartyl chlorine e6; Photodynamic therapy