Environment-Omics-Disease Research Center, China Medical University Hospital, China Medical University, Taichung, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
Department of Chemistry, National Chung Hsing University, Taichung, Taiwan.
Life Sci. 2021 Apr 15;271:119156. doi: 10.1016/j.lfs.2021.119156. Epub 2021 Feb 3.
Arecoline N-oxide (ANO), an oxidative metabolite of the areca nut, is a predictable initiator in carcinogenesis. The mechanisms of arecoline metabolites in human cancer specimens is still limited. This present study aims to estimate the oral squamous cell carcinoma (OSCC) inductive activity between arecoline metabolites in human cancer specimens/OSCC cells. We have collected 22 pairs (tumor and non-tumor part) of patient's specimens and checked for clinical characteristics. The identification of arecoline and its metabolites levels by using LC-MS/MS. The NOD/SCID mice model was used to check the OSCC inductive activity. The tumor part of OSCC samples exhibited higher levels of arecoline and ANO. Besides, ANO treated mice accelerates the NOTCH1, IL-17a and IL-1β expressions compared to the control mice. ANO exhibited higher cytotoxicity, intracellular ROS levels and decline in antioxidant enzyme levels in OC-3 cells. The protein expression of NOTCH1 and proliferation marker levels are significantly lower in NOM treated cells. Overall, ANO induced initial stage carcinogenesis in the oral cavity via inflammation, ROS and depletion of antioxidant enzymes. Arecoline N-oxide mercapturic acid (NOM) attenuates the initiation of oral carcinogenesis.
Arecoline N-oxide (ANO), 一种槟榔的氧化代谢物，是致癌作用的预测性启动剂。Arecoline 代谢物在人类癌症标本中的作用机制仍有限。本研究旨在评估人类癌症标本/口腔鳞状细胞癌 (OSCC) 细胞中的 Arecoline 代谢物的诱导活性。我们收集了 22 对（肿瘤和非肿瘤部分）患者标本，并检查了临床特征。使用 LC-MS/MS 鉴定 Arecoline 和其代谢物的水平。采用 NOD/SCID 小鼠模型检查 OSCC 诱导活性。OSCC 样本的肿瘤部分表现出更高水平的 Arecoline 和 ANO。此外，与对照组相比，ANO 处理的小鼠加速了 NOTCH1、IL-17a 和 IL-1β 的表达。ANO 在 OC-3 细胞中表现出更高的细胞毒性、细胞内 ROS 水平和抗氧化酶水平下降。经 NOM 处理的细胞中 NOTCH1 和增殖标记物的蛋白表达显著降低。总体而言，ANO 通过炎症、ROS 和抗氧化酶耗竭诱导口腔发生初始阶段的癌变。Arecoline N-oxide 巯基尿酸 (NOM) 可减轻口腔癌的发生。
