Betulinic acid: a new cytotoxic compound against malignant head and neck cancer cells.
Thurnher D , Turhani D , Pelzmann M , Wannemacher B , Knerer B , Formanek M , Wacheck V , Selzer E .
Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Vienna, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. dietmar.thrunher@univie.ac.at
BACKGROUND: A new compound, betulinic acid, has been found to be cytotoxic against a variety of tumor cells originating from the neural crest. Its efficacy against head and neck squamous cellular carcinoma cell lines has so far not been tested. METHODS: Cell numbers were assayed by automated counting; caspase activation and programmed cell death were determined using an antibody specific for an apoptosis-associated epitope in epithelial cells. The expression pattern of Bcl-2 family members was assessed by Western blotting. RESULTS: In two HNSCC cell lines betulinic acid induced apoptosis, which was characterized by a dose-dependent reduction in cell numbers, emergence of apoptotic cells, and an increase in caspase activity. Western blot analysis of the expression of various Bcl-2 family members in betulinic acid-treated cells showed, surprisingly, a suppression of the expression of the proapoptotic protein Bax but no changes in Mcl-1 or Bcl-2 expression. CONCLUSION: These data clearly demonstrate for the first time that betulinic acid has apoptotic activity against HNSCC cells. Copyright 2003 Wiley Periodicals, Inc. Head Neck 25: 732-740, 2003
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