Combined cytotoxic action of Viscum album agglutinin-1 and anticancer agents against human A549 lung cancer cells.
BACKGROUND
Viscum album agglutinin-1 (VAA-1) is assumed to be the biologically most active ingredient of misteltoe extracts that are often used as adjuvant cancer therapy. To develop new approaches for lung cancer treatment, we evaluated the antineoplastic activity of VAA-1 alone and in combination with other chemotherapeutic drugs, including doxorubicin, cisplatin and taxol in the human lung carcinoma cell line A549.


METHODS
Cytotoxicity was determined by 5-bromo-2'-deoxyuridine (BrdU) ELISA-assays and drug interaction assessed by the isobologram method. Analysis of cell cycle distribution was obtained using flow cytometry.


RESULTS
For all drug combinations tested the outcome was additive with the combination of VAA-1 and cycloheximide showing strong synergistic effects. Moreover, VAA-1 induced G1-phase accumulation mechanisms without causing apoptosis.


CONCLUSIONS
Our findings suggest that the simultaneous administration of VAA-1 with all anticancer agents tested is advantageous since cytotoxic effects are enhanced. These data may provide new clinicalperspectives in future mistletoe therapy.
Siegle
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Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie, Stuttgart, Germany.
Fritz
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McClellan
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Gutzeit
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Mürdter
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D000971:Antineoplastic Combined Chemotherapy Protocols / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D003513:Cycloheximide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D004357:Drug Synergism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D028321:Plant Preparations; D010940:Plant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D012276:Ricin / Q000008:administration & dosage; D014118:Toxins, Biological / Q000008:administration & dosage; D014407:Tumor Cells, Cultured
D028321:Plant Preparations; D010940:Plant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; C009674:ribosome inactivating protein, Viscum; D004317:Doxorubicin; D012276:Ricin; D003513:Cycloheximide; D017239:Paclitaxel; D002945:Cisplatin