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Betulinic acid: a new cytotoxic compound against malignant head and neck cancer cells.

Head & Neck

Antineoplastic Agents, Phytogenic, pharmacology, therapeutic use, Apoptosis, drug effects, Blotting, Western, Carcinoma, Squamous Cell, drug therapy, enzymology, pathology, Caspases, Cell Line, Tumor, Cell Survival, Head and Neck Neoplasms, Humans, Triterpenes

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      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. 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. 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. 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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