Park Su-Bin, Kwon Jung Woo, Rae Kim Hyung, Yu Hwa-Young, Hwan Kim Yong, Kim Junghyun
Department of Oral Pathology, School of Dentistry, Jeonbuk National University, Jeonju, Jeollabuk-do 54896, Republic of Korea.
Exp Ther Med. 2022 Jun 22;24(2):533. doi: 10.3892/etm.2022.11460. eCollection 2022 Aug.
Esculetin is a natural lactone that is commonly derived from coumarins. According to previous experiments using human cancer cells, esculetin has potent antitumor activity; it also inhibits proliferation and induces the apoptosis of cancer cells. In the present study, the anti-proliferative effect of esculetin on the submandibular salivary gland tumor cell line, A253, was evaluated via and analyses. Furthermore, the anti-cancer effects of esculetin in A253 cells and a xenograft model of salivary gland tumors were determined using 3-(4,5-dimethylthiazol)-2,5diphenyltetrazolium bromide and TUNEL assay, apoptosis protein array, quantitative polymerase chain reaction and western blot analysis. Esculetin (50-150 µM) was demonstrated to have an anti-proliferative effect in the A253 cell line ; this observed effect was dependent on the dose and duration of treatment. Esculetin also increased the levels of Bax, cleaved caspase-3, cleaved-9 and cleaved poly (ADP-ribose) polymerase apoptosis-related proteins, and decreased the expression levels of the Bcl-2 anti-apoptotic protein. With respect to apoptosis regulation, esculetin significantly decreased the proliferation of tumor cells in a xenograft model (100 mg/kg/day) for 18 days. Overall, esculetin could be a potential oral anticancer drug against salivary gland cancer.
七叶亭是一种常见的天然内酯，通常从香豆素中提取。根据先前使用人类癌细胞进行的实验，七叶亭具有强大的抗肿瘤活性；它还能抑制癌细胞增殖并诱导其凋亡。在本研究中，通过[具体实验方法1]和[具体实验方法2]分析评估了七叶亭对下颌下唾液腺肿瘤细胞系A253的抗增殖作用。此外，使用3-(4,5-二甲基噻唑)-2,5-二苯基四氮唑溴盐和TUNEL检测、凋亡蛋白阵列、定量聚合酶链反应和蛋白质免疫印迹分析，确定了七叶亭在A253细胞和唾液腺肿瘤异种移植模型中的抗癌作用。七叶亭（50 - 150 µM）在A253细胞系中显示出抗增殖作用；观察到的这种作用取决于治疗剂量和持续时间。七叶亭还增加了促凋亡蛋白Bax、裂解的半胱天冬酶-3、裂解的半胱天冬酶-9和裂解的聚（ADP-核糖）聚合酶的水平，并降低了抗凋亡蛋白Bcl-2的表达水平。在凋亡调节方面，七叶亭在异种移植模型（100 mg/kg/天）中显著降低了肿瘤细胞的增殖，持续18天。总体而言，七叶亭可能是一种潜在的抗唾液腺癌口服抗癌药物。
