Allyl Isothiocyanate Suppresses the Proliferation in Oral Squamous Cell Carcinoma via Mediating the KDM8/CCNA1 Axis.
Journal
Biomedicines
Journal Volume
11
Journal Issue
10
ISSN
2227-9059
Date Issued
2023-09-29
Author(s)
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
Chen, Yuan-Wu
Abstract
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.
Subjects
CCNA1
H3K36me2
KDM8/JMJD5
allyl isothiocyanate
oral cancer
patient-derived tumor xenograft (PDTX)
Type
journal article