Induction of Apoptosis in Human Oral Keratinocyte by Doxorubicin
Autor: | Hiroshi Sakagami, Hiroshi Oizumi, Satoshi Yokose, Yumiko Kanda, Yoshiko Masuda, Madoka Suguro, Takaaki Oizumi, Noriyuki Okudaira, Osamu Amano, Takenori Natori |
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Rok vydání: | 2017 |
Předmět: |
Keratinocytes
Cancer Research Periodontal Ligament Cell Gingiva Antineoplastic Agents Apoptosis Biology 01 natural sciences 03 medical and health sciences 0302 clinical medicine Microscopy Electron Transmission Cell Line Tumor Cell Adhesion medicine Humans Doxorubicin Fibroblast Cytotoxicity Caspase 3 Plant Extracts Cell growth General Medicine Fibroblasts Chromatin 0104 chemical sciences Plant Leaves 010404 medicinal & biomolecular chemistry medicine.anatomical_structure Oncology Cell culture 030220 oncology & carcinogenesis Immunology Cancer research Mouth Neoplasms Sasa Keratinocyte medicine.drug |
Zdroj: | Anticancer Research. 37:1023-1030 |
ISSN: | 1791-7530 0250-7005 |
Popis: | 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. |
Databáze: | OpenAIRE |
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