Butein is a flavonoid isolated from various medicinal plants. It is known to have different biological activities including anti-inflammation, anti-adipogenesis, and anti-angiogenesis. In the study, we demonstrated the anti-proliferative effect of butein in human osteosarcoma U-2 OS cells. Our data showed that butein significantly suppressed the viability and colony formation ability of U-2 OS cells. Further experiments revealed butein exposure resulted in a cell cycle arrest at S and G2/M phase in U-2 OS cells. Importantly, we found that butein activated the tumor suppressor p53, and trigged a p53-dependent senescence in U-2 OS cells. Knockdown of p53 suppressed the senescence and rescued the viability in butein-treated U-2 OS cells. Furthermore, we observed that butein exposure significantly enhanced reactive oxygen species (ROS) levels in U-2 OS cells. Co-administration of the ROS inhibitor NAC largely abolished the up-regulated p53 protein level, and rescued the suppressed viability and colony formation ability in butein-exposed U-2 OS cells. Taken together, our data proposed the increased ROS by butein exposure activated p53, and the activated p53 was involved in the anti-proliferative effect of butein via inducing senescence in U-2 OS cells. This report suggests that butein is a promising candidate for cancer therapy against osteosarcoma.

中文翻译：

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Butein 通过活性氧介导的骨肉瘤 U-2 OS 细胞中的 p53 激活诱导细胞衰老

Butein 是一种从各种药用植物中分离出来的黄酮类化合物。已知它具有不同的生物活性，包括抗炎、抗脂肪生成和抗血管生成。在这项研究中，我们证明了布丁素对人骨肉瘤 U-2 OS 细胞的抗增殖作用。我们的数据表明，butein 显着抑制了 U-2 OS 细胞的活力和集落形成能力。进一步的实验表明，在 U-2 OS 细胞中，暴露于丁二醇导致细胞周期停滞在 S 期和 G2/M 期。重要的是，我们发现butein 激活了肿瘤抑制因子p53，并在U-2 OS 细胞中触发了p53 依赖性衰老。p53 的敲低抑制了衰老并挽救了经布丁因处理的 U-2 OS 细胞的活力。此外，我们观察到 Butein 暴露显着提高了 U-2 OS 细胞中的活性氧 (ROS) 水平。ROS抑制剂NAC的共同给药在很大程度上消除了上调的p53蛋白水平，并挽救了暴露于butein的U-2 OS细胞中抑制的活力和集落形成能力。综上所述，我们的数据表明通过接触布丁因激活的 p53 增加了 ROS，并且活化的 p53 通过诱导 U-2 OS 细胞的衰老参与了布丁素的抗增殖作用。该报告表明，butein 是治疗骨肉瘤的一种有前途的候选药物。我们的数据表明，通过接触布丁因增加 ROS 激活了 p53，并且活化的 p53 通过诱导 U-2 OS 细胞衰老参与了布丁素的抗增殖作用。该报告表明，butein 是治疗骨肉瘤的一种有前途的候选药物。我们的数据表明，通过接触布丁因增加 ROS 激活了 p53，并且活化的 p53 通过诱导 U-2 OS 细胞衰老参与了布丁素的抗增殖作用。该报告表明，butein 是治疗骨肉瘤的一种有前途的候选药物。