PMID: 16716572 [PubMed - indexed for MEDLINE]
Combination of betulinic acid
with cisplatin--different cytotoxic effects in two head and neck cancer cell
lines.
Department
of Otorhinolaryngology, Head and Neck Surgery, Medical University of Vienna,
Waehringer Guertel 18-20, A-1090 Vienna, Austria.
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.
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