Induction of Apoptosis in Human Oral Keratinocyte by Doxorubicin.

Abstract:

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.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Sakagami H,Okudaira N,Masuda Y,Amano O,Yokose S,Kanda Y,Suguro M,Natori T,Oizumi H,Oizumi T

doi

10.21873/anticanres.11412

subject

Has Abstract

pub_date

2017-03-01 00:00:00

pages

1023-1029

issue

3

eissn

0250-7005

issn

1791-7530

pii

37/3/1023

journal_volume

37

pub_type

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