Hsieh Cheng-Chih, Yang Cheng-Yu, Peng Bo, Ho Sien-Lin, Tsao Chang-Huei, Lin Chih-Kung, Lin Chun-Shu, Lin Gu-Jiun, Lin Heng-Yi, Huang Hung-Chi, Chang Szu-Chien, Sytwu Huey-Kang, Chia Wei-Tso, Chen Yuan-Wu
Department of Pharmacy, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan.
School of Pharmacy and Institute of Pharmacy, National Defense Medical Center, Taipei 114, Taiwan.
Biomedicines. 2023 Sep 29;11(10):2669. doi: 10.3390/biomedicines11102669.
The dysregulated expression of cyclin genes can lead to the uncontrolled proliferation of cancer cells. Histone demethylase Jumonji-C domain-containing protein 5 (KDM8, JMJD5) and cyclin A1 (CCNA1) are pivotal in cell cycle progression. A promising candidate for augmenting cancer treatment is Allyl isothiocyanate (AITC), a natural dietary chemotherapeutic and epigenetic modulator. This study aimed to investigate AITC's impact on the KDM8/CCNA1 axis to elucidate its role in oral squamous cell carcinoma (OSCC) tumorigenesis. The expression of KDM8 and CCNA1 was assessed using a tissue microarray (TMA) immunohistochemistry (IHC) assay. In vitro experiments with OSCC cell lines and in vivo experiments with patient-derived tumor xenograft (PDTX) and SAS subcutaneous xenograft tumor models were conducted to explore AITC's effects on their expression and cell proliferation. The results showed elevated KDM8 and CCNA1 levels in the OSCC patient samples. AITC exhibited inhibitory effects on OSCC tumor growth in vitro and in vivo. Additionally, AITC downregulated KDM8 and CCNA1 expression while inducing histone H3K36me2 expression in oral cancer cells. These findings underscore AITC's remarkable anticancer properties against oral cancer, highlighting its potential as a therapeutic option for oral cancer treatment by disrupting the cell cycle by targeting the KDM8/CCNA1 axis.
细胞周期蛋白基因的表达失调可导致癌细胞的失控增殖。组蛋白去甲基化酶含Jumonji-C结构域蛋白5（KDM8，JMJD5）和细胞周期蛋白A1（CCNA1）在细胞周期进程中起关键作用。异硫氰酸烯丙酯（AITC）是一种天然的饮食化疗药物和表观遗传调节剂，是增强癌症治疗效果的一个有前景的候选药物。本研究旨在探讨AITC对KDM8/CCNA1轴的影响，以阐明其在口腔鳞状细胞癌（OSCC）肿瘤发生中的作用。使用组织微阵列（TMA）免疫组织化学（IHC）分析评估KDM8和CCNA1的表达。进行了OSCC细胞系的体外实验以及患者来源肿瘤异种移植（PDTX）和SAS皮下异种移植肿瘤模型的体内实验，以探究AITC对它们表达和细胞增殖的影响。结果显示OSCC患者样本中KDM8和CCNA1水平升高。AITC在体外和体内均对OSCC肿瘤生长表现出抑制作用。此外，AITC下调口腔癌细胞中KDM8和CCNA1的表达，同时诱导组蛋白H3K36me2的表达。这些发现强调了AITC对口腔癌具有显著的抗癌特性，突出了其通过靶向KDM8/CCNA1轴破坏细胞周期而作为口腔癌治疗选择的潜力。
