Background/Aim: We have previously reported that
doxorubicin (DXR) showed much higher cytotoxicity against
human oral squamous cell carcinoma cell lines compared to
normal human mesenchymal normal oral cells (gingival
fibroblast, periodontal ligament fibroblast, pulp cell), yielding
high tumor-specificity. However, we unexpectedly found that
doxorubicin showed potent cytotoxicity against human normal
oral keratinocytes and primary gingival epithelial cells. In the
present study, we investigated the reproducibility, underlining
mechanisms and generality of this unexpected finding. Materials
and Methods: Viable cell number was determined by the 3-(4,5-
dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method,
fine cell structure by transmission electron microscopy and
apoptosis induction by western blot analysis. Results:
Doxorubicin induced keratinocyte toxicity, regardless of cell
density and concentration of FBS in the culture medium.
Doxorubicin induced apoptosis (characterized by the loss of cell
surface microvilli, chromatin condensation, nuclear
fragmentation and caspase-3 activation) in keratinocytes. A total
of 11 anticancer drugs showed similar keratinocyte toxicity.
Alkaline extract of the leaves of Sasa senanensis Rehder partially
alleviated the DXR-induced keratinocyte cytotoxicity by promoting cell growth. Conclusion: The present study suggested
that oral keratinocyte toxicity is a novel adverse effect of most
anticancer agents.