Induction of Apoptosis in Human Oral Keratinocyte by Doxorubicin
Induction of Apoptosis in Human Oral Keratinocyte by Doxorubicin
复制标题
DOI：
10.21873/anticanres.11412
复制
发表时间：
2017-03-01
影响因子：
2
通讯作者：
Oizumi, Takaaki
中科院分区：
文献类型：
--
作者：
Sakagami, Hiroshi;Okudaira, Noriyuki;Oizumi, Takaaki
背景/目的：我们之前报道过，与正常的人间充质正常口腔细胞（牙龈成纤维细胞、牙周韧带成纤维细胞、牙髓细胞）相比，多柔比星（DXR）对人口腔鳞状细胞癌细胞具有更高的细胞毒性，具有较高的肿瘤特异性。然而，我们意外地发现，阿霉素对人类正常口腔角质形成细胞和原代牙龈上皮细胞显示出强大的细胞毒性。在本研究中，我们研究了这一意外发现的可重复性、潜在机制和普遍性。材料与方法：采用3-（4,5二甲基噻唑-2 -基）-2,5二苯基溴化四唑法测定活细胞数，透射电镜观察细胞细部结构，western blot检测细胞凋亡诱导。结果：无论细胞密度和培养液中FBS的浓度如何，阿霉素都能诱导角质细胞毒性。阿霉素诱导角质形成细胞凋亡（特征为细胞表面微绒毛丢失、染色质凝聚、核断裂和caspase-3活化）。共有11种抗癌药物表现出类似的角化细胞毒性。山沙叶碱性提取物通过促进细胞生长，部分减轻了dxr诱导的角化细胞毒性。结论：口服角化细胞毒性是大多数抗癌药物新的不良反应。
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-(4,5dimethylthiazol- 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.