title: Photochemical internalization of bleomycin and temozolomide--in vitro studies on the glioma cell line F98.
abstract: Here we evaluate the photosensitizer meso-tetraphenyl chlorin disulphonate (TPCS2a) in survival studies of rat glioma cancer cells in combination with the novel photochemical internalization (PCI) technique. The tested anticancer drugs were bleomycin (BLM) and temozolomide (TMZ). Glioma cells were incubated with TPCS2a (0.2 μg ml(-1), 18 h, 37 °C) before BLM or TMZ stimulation (4 h) prior to red light illumination (652 nm, 50 mW cm(-2)). The cell survival after BLM (0.5 μm)-PCI (40 s light) quantified using the MTT assay was reduced to about 25% after 24 h relative to controls, and to 31% after TMZ-PCI. The supplementing quantification by clonogenic assays, using BLM (0.1 μm), indicated a long-term cytotoxic effect: the surviving fraction of clonogenic cells was reduced to 5% after light exposure (80 s) with PCI, compared to 70% in the case of PDT. In parallel, structural and morphological changes within the cells upon light treatment were examined using fluorescence microscopy techniques. The present study demonstrates that PCI of BLM is an effective method for killing F98 glioma cells, but smaller effects were observed using TMZ following the "light after" strategy. The results are the basis for further in vivo studies on our rat glioma cancer model using PDT and PCI.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, N-7489 Trondheim, Norway.
authors.forename: Odrun A
authors.initials: OA
authors.lastname: Gederaas
authors.forename: Anette
authors.initials: A
authors.lastname: Hauge
authors.forename: Pål G
authors.initials: PG
authors.lastname: Ellingsen
authors.forename: Kristian
authors.initials: K
authors.lastname: Berg
authors.forename: Dag
authors.initials: D
authors.lastname: Altin
authors.forename: Tora
authors.initials: T
authors.lastname: Bardal
authors.forename: Anders
authors.initials: A
authors.lastname: Høgset
authors.forename: Mikael
authors.initials: M
authors.lastname: Lindgren
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism*; D001761:Bleomycin / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D005910:Glioma / Q000378:metabolism*; D008027:Light; D015394:Molecular Structure; D055668:Photochemical Processes; D017319:Photosensitizing Agents / Q000494:pharmacology; D011166:Porphyrins / Q000494:pharmacology; D051381:Rats; D000077204:Temozolomide; D014410:Tumor Stem Cell Assay
chemical_list: D000970:Antineoplastic Agents; D017319:Photosensitizing Agents; D011166:Porphyrins; C559366:meso-tetraphenyl chlorin disulphonate; D001761:Bleomycin; D003606:Dacarbazine; D000077204:Temozolomide