BACKGROUND: We recently reported that a cranberry proanthocyanidin rich extract (C-PAC) induces autophagic cell death in apoptotic resistant esophageal adenocarcinoma (EAC) cells and necrosis in autophagy resistant cells. EAC is characterized by high morbidity and mortality rates supporting development of improved preventive interventions. OBJECTIVE: The current investigation sought to investigate the role of reactive oxygen species (ROS) in the context of C-PAC induced cell death. METHODS: A panel of human esophageal cell lines of EAC or BE (Barrett’s esophagus) origin were treated with C-PAC and assessed for ROS modulation using CellROX® Green reagent and the Amplex Red assay to specifically measure hydrogen peroxide levels. RESULTS: C-PAC significantly increased ROS levels in EAC cells, but significantly reduced ROS levels in CP-C BE cells. Increased hydrogen peroxide levels were also detected in C-PAC treated EAC cells and supernatant; however, hydrogen peroxide levels were significantly increased in medium alone, without cells, suggesting that C-PAC interferes or directly acts on the substrate. Hydrogen peroxide levels did not change in C-PAC treated CP-C BE cells. CONCLUSION: These experiments provide additional mechanistic insight regarding C-PAC induced cancer cell death through modulation of ROS. Additional research is warranted to identify specific ROS species associated with C-PAC exposure.

中文翻译：

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蔓越莓原花青素调节巴雷特和食管腺癌细胞系中的活性氧

背景：我们最近报道了蔓越莓原花青素丰富提取物 (C-PAC) 诱导凋亡抗性食管腺癌 (EAC) 细胞的自噬细胞死亡和自噬抗性细胞的坏死。EAC 的特点是发病率和死亡率高，支持开发改进的预防干预措施。目的：目前的调查旨在研究活性氧 (ROS) 在 C-PAC 诱导细胞死亡的背景下的作用。方法：一组 EAC 或 BE（巴雷特食管）来源的人食管细胞系用 C-PAC 处理，并使用 CellROX® Green 试剂和 Amplex Red 测定评估 ROS 调节，以专门测量过氧化氢水平。结果：C-PAC 显着增加了 EAC 细胞中的 ROS 水平，但显着降低了 CP-C BE 细胞中的 ROS 水平。在 C-PAC 处理的 EAC 细胞和上清液中也检测到过氧化氢水平增加；然而，在没有细胞的单独培养基中过氧化氢水平显着增加，表明 C-PAC 干扰或直接作用于底物。过氧化氢水平在 C-PAC 处理的 CP-C BE 细胞中没有变化。结论：这些实验提供了关于 C-PAC 通过调节 ROS 诱导癌细胞死亡的额外机制见解。需要额外的研究来确定与 C-PAC 暴露相关的特定 ROS 种类。过氧化氢水平在 C-PAC 处理的 CP-C BE 细胞中没有变化。结论：这些实验提供了关于 C-PAC 通过调节 ROS 诱导癌细胞死亡的额外机制见解。需要额外的研究来确定与 C-PAC 暴露相关的特定 ROS 种类。过氧化氢水平在 C-PAC 处理的 CP-C BE 细胞中没有变化。结论：这些实验提供了关于 C-PAC 通过调节 ROS 诱导癌细胞死亡的额外机制见解。需要额外的研究来确定与 C-PAC 暴露相关的特定 ROS 种类。