PT  - JOURNAL ARTICLE
AU  - HIROSHI SAKAGAMI
AU  - NORIYUKI OKUDAIRA
AU  - YOSHIKO MASUDA
AU  - OSAMU AMANO
AU  - SATOSHI YOKOSE
AU  - YUMIKO KANDA
AU  - MADOKA SUGURO
AU  - TAKENORI NATORI
AU  - HIROSHI OIZUMI
AU  - TAKAAKI OIZUMI
TI  - Induction of Apoptosis in Human Oral Keratinocyte by Doxorubicin
DP  - 2017 Mar 01
TA  - Anticancer Research
PG  - 1023--1029
VI  - 37
IP  - 3
4099  - http://ar.iiarjournals.org/content/37/3/1023.short
4100  - http://ar.iiarjournals.org/content/37/3/1023.full
SO  - Anticancer Res2017 Mar 01; 37
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.