Dept. Environmental Carcinogenesis & Toxicology, Chittaranjan National Cancer Institute, 37, S P Mukherjee Road, Kolkata 700019, India.
Dept. Environmental Carcinogenesis & Toxicology, Chittaranjan National Cancer Institute, 37, S P Mukherjee Road, Kolkata 700019, India.
Toxicol In Vitro. 2022 Dec;85:105478. doi: 10.1016/j.tiv.2022.105478. Epub 2022 Sep 16.
A major global problem is chronic exposure to inorganic arsenic (iAs) which causes various health hazards including cancer. Escalation of reactive oxygen species (ROS) generation by chronic iAs exposure promotes Epithelial to Mesenchymal transition (EMT) which is followed by metastatic progression. In the present study, skin keratinocyte cells (HaCaT) were divided into three groups: (i) untreated, (ii) chronically iAs exposed, (iii) black tea extract (BTE) along with iAs treated. ROS was estimated by flowcytometry, expression of EMT markers were assessed by flowcytometry, western-blotting and Immunofluorescence. For metastatic studies, wound-healing assay, gelatin zymography, western-blot, transwell migration/invasion assay had been performed. Long term exposure of HaCaT cells to iAs causes excess generation of ROS. Morphological transformation and EMT were apparent at 210 days of exposure. Development of metastatic characteristics were observed at 240 days. Alterations in the parameters induced by iAs were found to be ameliorated by BTE. BTE was found to quench excess generation of ROS by iAs, subsequently inhibiting the chain of events like EMT and metastasis. Therefore, BTE may be considered as a potential phytochemical to prevent the deleterious effect of iAs. Skin carcinogenesis induced by iAs may thus be prevented by BTE via inhibition of EMT.
一个全球性的主要问题是慢性暴露于无机砷（iAs），这会导致各种健康危害，包括癌症。慢性 iAs 暴露会引发活性氧（ROS）的大量生成，从而促进上皮间质转化（EMT），随后导致转移进展。在本研究中，皮肤角质形成细胞（HaCaT）被分为三组：（i）未处理组，（ii）慢性 iAs 暴露组，（iii）红茶提取物（BTE）联合 iAs 处理组。通过流式细胞术估计 ROS，通过流式细胞术、Western blot 和免疫荧光评估 EMT 标志物的表达。为了进行转移研究，进行了划痕愈合试验、明胶酶谱分析、Western blot、Transwell 迁移/侵袭试验。HaCaT 细胞长期暴露于 iAs 会导致 ROS 的过度生成。暴露 210 天后出现明显的形态转化和 EMT。在 240 天时观察到转移特征的发展。iAs 诱导的参数变化被发现可以通过 BTE 得到改善。BTE 被发现可以抑制 iAs 引起的 ROS 的过度生成，从而抑制 EMT 和转移等一系列事件。因此，BTE 可能被认为是一种潜在的植物化学物质，可以预防 iAs 的有害影响。BTE 可能通过抑制 EMT 来预防 iAs 诱导的皮肤癌变。
