Tumor-specificity (TS) and anti-inflammatory
activity of benzo[b]cyclohept[e][1,4]oxazin-6(11H)-one,
generally known as benzoxazinotropone (BOT), have been
reported. In order to find a new biological activity, the
combination effect of BOT and three apoptosis-inducing
agents was investigated. Cytotoxicity against four human
oral squamous cell carcinoma (OSCC) cell lines and five
human oral normal cells (gingival fibroblasts, periodontal
ligament fibroblasts, pulp cells, oral keratinocytes and
primary gingival epithelial cells) was determined by 3-(4,5-
dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
method. TS was evaluated by the ratio of the mean 50%
cytotoxic concentration (CC50) against normal oral cells to
the one against OSCC cell lines. Synergy was evaluated by
CompuSyn software program. Expression of cleaved forms
of poly ADP-ribose polymerase and caspsase-3 was
evaluated by western blot analysis. BOT induced activation
of caspase 3, suggesting the apoptosis induction in HSC-2
OSCC cells. BOT enhanced the cytotoxicity of doxorubicin
(DXR) additively and that of curcumin and resveratrol
synergistically. On the other hand, BOT did not enhance, but
rather inhibit the cytotoxicity of DXR against normal
keratinocytes. The present study suggests that BOT may
enhance the anti-tumor activity of apoptosis-inducing agents,
while reducing its cytotoxicity against normal cells.