RT Journal Article
SR Electronic
T1 Induction of Apoptosis in Human Oral Keratinocyte by Doxorubicin
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 1023
OP 1029
VO 37
IS 3
A1 HIROSHI SAKAGAMI
A1 NORIYUKI OKUDAIRA
A1 YOSHIKO MASUDA
A1 OSAMU AMANO
A1 SATOSHI YOKOSE
A1 YUMIKO KANDA
A1 MADOKA SUGURO
A1 TAKENORI NATORI
A1 HIROSHI OIZUMI
A1 TAKAAKI OIZUMI
YR 2017
UL http://ar.iiarjournals.org/content/37/3/1023.abstract
AB 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.