title: Hematoporphyrin derivative and anthracyclines mutually inhibit cellular uptake and toxicity.
abstract: Hematoporphyrin derivative (HpD) is a fluorescent photosensitizer which localizes selectively in tumors and is used in photoirradiation therapy of various types of cancer. Photoirradiation is a local form of treatment. There may be advantages in combining it with systemic chemotherapy, and we therefore studied the interaction of HpD and various cytotoxic drugs [daunorubicin (DR), adriamycin (AD), mitozantrone (MI), cis-platinum (CP) and 5-fluorouracil (FU)] with respect to cellular uptake and toxicity. Cultured cells were incubated with HpD and the cytotoxic drugs, either simultaneously or sequentially. The amount of DR, AD and HpD taken up by cells was quantitated by measuring cellular fluorescence and by determining the specific cytotoxic action of the drugs (light-induced cell kill for HpD and loss of proliferative potential for the cytotoxic drugs). The presence of 100 mg/l HpD during drug incubation caused 30-, 12- and 6-fold reductions in the cytotoxicity of DR, AD and MI respectively. HpD-associated fluorescence and photosensitization were reduced upon co-incubation of cells with HpD and AD. When cells were incubated with HpD and AD sequentially, fluorescence was equal to the sum of fluorescence values achieved by treatment with HpD and AD alone, and the cytotoxicity was not reduced. This suggests that the effects were due to an interaction of HpD with the drugs outside the cells, resulting in a reduction of free drug available for cellular uptake. CP and FU did not interact with HpD. The results suggest that protocols which combine photoirradiation therapy and chemotherapy with anthracyclines or similar compounds need to take this interaction into account.
mesh_terms: D000818:Animals; D002469:Cell Separation; D002478:Cells, Cultured; D002945:Cisplatin / Q000633:toxicity*; D006224:Cricetinae; D003630:Daunorubicin / Q000633:toxicity*; D004317:Doxorubicin / Q000633:toxicity*; D004347:Drug Interactions; D005260:Female; D005434:Flow Cytometry; D005472:Fluorouracil / Q000633:toxicity*; D006414:Hematoporphyrin Photoradiation; D010778:Photochemotherapy
chemical_list: D004317:Doxorubicin; D002945:Cisplatin; D005472:Fluorouracil; D003630:Daunorubicin