Synergism between rViscumin and cisplatin is not dependent on ERCC-1 expression.
Interactions between recombinant mistletoe lectin (rViscumin) and anticancer drugs were investigated in vitro. rViscumin enhanced the cytotoxic effects of vincristine, mafosfamide, idarubicin and cisplatin in the human leukemia cell lines K562 and KG1a. In human marrow progenitor cells, rViscumin inhibited colony formation and did not exert any protective activity against cisplatin-induced inhibition of clonogenicity. Quantitative real-time reverse transcription polymerase chain reaction analysis revealed that cisplatin treatment of K562 cells resulted in a 1.9-fold increase in mRNA expression of the nucleotide excision repair gene ERCC-1. This upregulation was not prevented when cells were post-incubated with rViscumin. Our study provides evidence that rViscumin is capable of enhancing cytotoxicity of anticancer agents in vitro. This synergism appears to be independent of transcriptional activity of DNA repair relevant genes.
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D020137:Base Pair Mismatch; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004260:DNA Repair; D004268:DNA-Binding Proteins; D004357:Drug Synergism; D004720:Endonucleases; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D028321:Plant Preparations / Q000494:pharmacology*; D010940:Plant Proteins; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm; D020133:Reverse Transcriptase Polymerase Chain Reaction; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D028321:Plant Preparations; D010940:Plant Proteins; D011506:Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; C009674:ribosome inactivating protein, Viscum; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin