Britanin, a natural pseudoguaiacane sesquiterpene lactone, has significant antioxidant and anti-inflammatory activity, but little is known about its tumor inhibitory activity and the underlying mechanism. Here, we demonstrated in vitro and in vivo that britanin inhibited the growth of human prostate cancer cell lines (PC-3, PC-3-LUC, and DU-145). Through in vitro study, the results showed that britanin significantly decreased cell proliferation, migration, and motility. The moderate toxicity of britanin was determined with an acute toxicity study. A luciferase-labeled animal tumor xenograft model and bioluminescence imaging were applied, combining with biological validation for assessing the tumor progression. In vivo results demonstrated that britanin inhibited the growth of PC-3-LUC. The interleukin-2 level in mice was upregulated by britanin, which indicated that britanin induced antitumor immune activation. In addition, britanin downregulated the expression of nuclear factor (NF)-κB p105/p50, pp65, IκBα, pIκBα, phosphoinositide 3-kinase, pPI3k, Akt (protein kinase B, PKB), and pAkt proteins and upregulated expression of Bax. We discovered that britanin inhibits the growth of prostate cancer cells both in vitro and in vivo by regulating PI3K/Akt/NF-κB-related proteins and activating immunity. These findings shed light on the development of britanin as a promising agent for prostate cancer therapy.

中文翻译：

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Britanin 通过 PI3K/Akt/NF-κB 信号通路对人前列腺癌细胞系表现出潜在的抑制活性

Britanin 是一种天然的假愈创木瓜倍半萜内酯，具有显着的抗氧化和抗炎活性，但对其肿瘤抑制活性和潜在机制知之甚少。在这里，我们在体外和体内证明了 britanin 抑制人前列腺癌细胞系（PC-3、PC-3-LUC 和 DU-145）的生长。通过体外研究，结果表明，britanin 显着降低细胞增殖、迁移和运动。Britanin 的中度毒性是通过急性毒性研究确定的。应用荧光素酶标记的动物肿瘤异种移植模型和生物发光成像，结合生物学验证来评估肿瘤进展。体内结果表明，britanin 抑制了 PC-3-LUC 的生长。小鼠的白细胞介素 2 水平被 britanin 上调，这表明britanin诱导了抗肿瘤免疫激活。此外，britanin 下调核因子 (NF)-κB p105/p50、pp65、IκBα、pIκBα、磷酸肌醇 3-激酶、pPI3k、Akt（蛋白激酶 B，PKB）和 pAkt 蛋白的表达并上调 Bax 的表达。我们发现 britanin 通过调节 PI3K/Akt/NF-κB 相关蛋白和激活免疫抑制体外和体内前列腺癌细胞的生长。这些发现阐明了 britanin 作为前列腺癌治疗的有前途的药物的发展。我们发现 britanin 通过调节 PI3K/Akt/NF-κB 相关蛋白和激活免疫抑制体外和体内前列腺癌细胞的生长。这些发现阐明了 britanin 作为前列腺癌治疗的有前途的药物的发展。我们发现 britanin 通过调节 PI3K/Akt/NF-κB 相关蛋白和激活免疫抑制体外和体内前列腺癌细胞的生长。这些发现阐明了 britanin 作为前列腺癌治疗的有前途的药物的发展。