Hiroshi Sakagami1,2, Noriyuki Okudaira3, Yoshiko Masuda2, Osamu Amano4, Satoshi Yokose5, Yumiko Kanda6, Madoka Suguro7, Takenori Natori7, Hiroshi Oizumi7, Takaaki Oizumi7. 1. Division of Pharmacology, Meikai University School of Dentistry, Sakado, Japan sakagami@dent.meikai.ac.jp takaakio@daiwaseibutsu.co.jp. 2. Meikai Pharmaco-Medical Laboratory (MPL), Meikai University School of Dentistry, Sakado, Japan. 3. Division of Pharmacology, Meikai University School of Dentistry, Sakado, Japan. 4. Division of Anatomy, Meikai University School of Dentistry, Sakado, Japan. 5. Division of Endodontics, Meikai University School of Dentistry, Sakado, Japan. 6. Department of Electron Microscope, Meikai University, School of Dentistry, Sakado, Japan. 7. Daiwa Biological Research Institute Co, Ltd., Kanagawa, Japan.
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. Copyright
BACKGROUND/AIM: We have previously reported that doxorubicin (DXR) showed much higher cytotoxicity against humanoral 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. Copyright
Authors: Praveen K Roayapalley; Hiroshi Sakagami; Keitaro Satoh; Shigeru Amano; Kenjiro Bandow; Renato J Aguilera; Karla G Cano Hernandez; Austre Y Schiaffino Bustamante; Stephen G Dimmock; Rajendra K Sharma; Umashankar Das; Jonathan R Dimmock Journal: Medicines (Basel) Date: 2021-12-16