title: Combination of betulinic acid with cisplatin--different cytotoxic effects in two head and neck cancer cell lines.
abstract: Betulinic acid (BetA), a new experimental cytotoxic compound that is active against human melanoma cells and neuroectodermal tumor cells, has recently been shown to be also effective against head and neck squamous carcinoma cells (HNSCC). In this study we investigated BetA in combination with cisplatin in squamous cell carcinoma cell lines of the tongue. SCC25 and SCC9 were treated with BetA and/or cisplatin. Cells were counted with an automated analyzing system. Caspase activation was determined using the M30 Cyto-Death ELISA, expression of the anti-apoptotic protein Mcl-1 by Western blot analysis. Visualization of apoptotic cells was achieved by immunohistochemistry. Synergistic cytotoxic effect and the induction of apoptosis under combined treatment was observed in SCC25 cells only after 24 or 48 h, whereas treatment of SCC25 cells for 72 h with BetA and cisplatin showed antagonism or subadditive effects. In SCC9 cells, antagonism occurred over an increase of dose and time during treatment. Furthermore, we could not demonstrate a significant alteration in the expression of the anti-apoptotic protein, Mcl-1. Our in vitro data demonstrate that BetA seems to be an unlikely candidate for combination with cisplatin in the treatment of head and neck cancer.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: Christina
authors.initials: C
authors.lastname: Eder-Czembirek
authors.forename: Cornelia
authors.initials: C
authors.lastname: Czembirek
authors.forename: Boban M
authors.initials: BM
authors.lastname: Erovic
authors.forename: Edgar
authors.initials: E
authors.lastname: Selzer
authors.forename: Dritan
authors.initials: D
authors.lastname: Turhani
authors.forename: Laurenz
authors.initials: L
authors.lastname: Vormittag
authors.forename: Dietmar
authors.initials: D
authors.lastname: Thurnher
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology; D006801:Humans; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000378:metabolism; D053978:Pentacyclic Triterpenes; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013997:Time Factors; D014315:Triterpenes / Q000494:pharmacology*; D000094062:Betulinic Acid
chemical_list: D000970:Antineoplastic Agents; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D053978:Pentacyclic Triterpenes; D019253:Proto-Oncogene Proteins c-bcl-2; D014315:Triterpenes; D020169:Caspases; D002945:Cisplatin; D000094062:Betulinic Acid