Jung Minjung, Han Dae Jin, Ahn Chi-Hyun, Hong Kyoung-Ok, Choi Youn Soo, Kim Jun Sung, Yoon Hye-Jung, Hong Seong Doo, Shin Ji-Ae, Cho Sung-Dae
Department of Oral Pathology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 03080, Republic of Korea.
School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea.
Oncol Rep. 2021 Jun;45(6). doi: 10.3892/or.2021.8054. Epub 2021 Apr 28.
Mitotic catastrophe, a cell death mechanism characterized by abnormal mitosis, has been regarded as a therapeutic approach for the development of anti‑cancer drug candidates. The aim of the present study was to investigate the potential effect of the ethanolic extract of (EEJS) on the occurrence of mitotic catastrophe in human oral cancer cell lines. The effect of EEJS on the occurrence of mitotic catastrophe was evaluated by measuring cytotoxicity, observing phase‑contrast or transmission electron microscope findings, evaluating the appearance of microtubule or chromosome abnormalities, and detecting the phosphorylation of histone H3 (Ser). The apoptotic effect of EEJS was assessed by detecting cleaved PARP, analyzing the sub‑G population, Annexin V‑FITC/PI double staining, western blot analysis, and the transient transfection of myeloid cell leukemia‑1 (Mcl‑1) overexpression vectors. EEJS treatment was effective in inhibiting cell proliferation in human oral cancer cell lines. EEJS resulted in the enrichment of enlarged multinucleated cells, the disturbance of microtubule formation, and increased phosphorylation of histone H3 (Ser), which demonstrates the occurrence of mitotic catastrophe. Additionally, the multinucleated cells underwent apoptotic cell death in a cell context‑dependent manner, which was associated with the reduction of Mcl‑1 protein levels. Findings of the present study indicate that EEJS could be effective for treating human oral cancer by promoting mitotic catastrophe linked to apoptotic cell death.
有丝分裂灾难是一种以异常有丝分裂为特征的细胞死亡机制,已被视为开发抗癌候选药物的一种治疗方法。本研究的目的是探讨鸦胆子乙醇提取物(EEJS)对人口腔癌细胞系中有丝分裂灾难发生的潜在影响。通过测量细胞毒性、观察相差显微镜或透射电子显微镜结果、评估微管或染色体异常的出现以及检测组蛋白H3(Ser)的磷酸化来评估EEJS对有丝分裂灾难发生的影响。通过检测裂解的PARP、分析亚G期群体、Annexin V-FITC/PI双染、蛋白质免疫印迹分析以及髓系细胞白血病-1(Mcl-1)过表达载体的瞬时转染来评估EEJS的凋亡作用。EEJS处理可有效抑制人口腔癌细胞系中的细胞增殖。EEJS导致多核大细胞增多、微管形成紊乱以及组蛋白H3(Ser)磷酸化增加,这表明有丝分裂灾难的发生。此外,多核细胞以细胞背景依赖的方式发生凋亡性细胞死亡,这与Mcl-1蛋白水平的降低有关。本研究结果表明,EEJS可通过促进与凋亡性细胞死亡相关的有丝分裂灾难来有效治疗人类口腔癌。