Potentiation of photodynamic therapy with hypericin by mitomycin C in the radiation-induced fibrosarcoma-1 mouse tumor model.
Hypericin, a polycyclic quinone obtained from plants of the genus Hypericum, has been shown to be a promising photosensitizer. We investigated the combination of hypericin-photodynamic therapy (PDT) and a bioreductive drug mitomycin C (MMC) in the present study. The radiation-induced fibrosarcoma-1 tumors were exposed to laser light (120 J/cm2 at 595 nm) 24 h after an intravenous injection of hypericin (1 mg/kg). Hypericin-PDT alone significantly decreased tumor perfusion and oxygen tension as demonstrated by India ink staining technique and OxyLite pO2 measurement, respectively. The in vivo-in vitro cell-survival assay revealed about 60% direct tumor cell killing immediately after PDT. No significant delayed tumor cell death was observed after PDT, which suggests that vascular damage does not contribute significantly to the overall tumor cell death. Injection of a 2.5 mg/kg dose of MMC 20 min before light application significantly decreased tumor cell survival and delayed tumor growth compared with PDT or MMC alone. No greater skin reaction was observed after the combination of MMC and PDT than after PDT alone. Our study demonstrates that combining hypericin-PDT with MMC can be effective in enhancing tumor response with little side effect.
Chen
Bin
B
Laboratory of Pharmaceutical Biology and Phytopharmacology, Faculty of Pharmaceutical Sciences, Katholieke Universiteit Leuven, Van Evenstraat 4, B-3000, Leuven, Belgium.
Ahmed
Bissan
B
Landuyt
Willy
W
Ni
Yicheng
Y
Gaspar
Robert
R
Roskams
Tania
T
de Witte
Peter A
PA
D000818:Animals; D000873:Anthracenes; D004195:Disease Models, Animal; D004357:Drug Synergism; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy*; D051379:Mice; D016685:Mitomycin / Q000494:pharmacology* / Q000627:therapeutic use; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use
D000873:Anthracenes; D016685:Mitomycin; D010569:Perylene; C004965:hypericin