School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
Toxicol Appl Pharmacol. 2018 Mar 1;342:1-13. doi: 10.1016/j.taap.2018.01.011. Epub 2018 Feb 4.
Burkitt's lymphoma (BL) is a highly aggressive B-cell non-Hodgkin lymphoma with rapid growth and dissemination propensity. Triptolide (TP), an active component extracted from Chinese herb Tripterygium wilfordii Hook f., has broad-spectrum anti-tumor activities. This study aimed to explore the in vitro and in vivo anti-cancer effects of TP on BL and the potential molecular mechanisms. In this study, the in vitro anti-tumor activity of TP was determined by CCK-8 and flow cytometry assays in Raji, NAMALWA and Daudi cells. The expression of SIRT3, phosphorylation and acetylation of glycogen synthase kinase-3β (GSK-3β) were analyzed by Western blot assay. Moreover, we examined the mitochondrial membrane potential by JC-1 method and measured apoptosis related protein using Western blot assay. BL xenograft model in NOD/SCID mice were established to evaluate the in vivo anti-cancer effect of TP. We discovered that TP inhibited BL cell growth and induced apoptosis in a dose-dependent manner. Loss of SIRT3 provides growth advances for BL cells. However, TP could up-regulate SIRT3 expression, which resulted in suppression of BL cells proliferation. GSK-3β was activated by SIRT3-mediated deacetylation, which subsequently induced mitochondrial translocation and accumulation of Bax and decrease of mitochondrial membrane potential. Anti-tumor studies in vivo showed that TP (0.36 mg/kg) inhibited the growth of BL xenografts in NOD/SCID mice with an inhibitory rate of 73.13%. Our data revealed that TP triggered mitochondrial apoptotic pathway in BL by increasing SIRT3 expression and activating SIRT3/GSK-3β/Bax pathway. This study indicated that TP is a potential anti-cancer Chinese herbal medicine against BL.
伯基特淋巴瘤（BL）是一种具有快速生长和扩散倾向的高度侵袭性 B 细胞非霍奇金淋巴瘤。雷公藤红素（TP）是从中药雷公藤中提取的一种有效成分，具有广谱抗肿瘤活性。本研究旨在探讨 TP 对 BL 的体外和体内抗癌作用及其潜在的分子机制。在这项研究中，通过 CCK-8 和流式细胞术检测 Raji、NAMALWA 和 Daudi 细胞中 TP 的体外抗肿瘤活性。通过 Western blot 检测 SIRT3 的表达、磷酸化和糖原合酶激酶-3β（GSK-3β）的乙酰化。此外，我们通过 JC-1 法检测线粒体膜电位，通过 Western blot 检测凋亡相关蛋白。建立 NOD/SCID 小鼠 BL 移植瘤模型，评价 TP 的体内抗癌作用。我们发现 TP 呈剂量依赖性抑制 BL 细胞生长并诱导细胞凋亡。SIRT3 的缺失为 BL 细胞的生长提供了优势。然而，TP 可以上调 SIRT3 的表达，从而抑制 BL 细胞的增殖。GSK-3β 通过 SIRT3 介导的去乙酰化而被激活，随后导致线粒体易位和 Bax 的积累以及线粒体膜电位的降低。体内抗肿瘤研究表明，TP（0.36mg/kg）抑制 NOD/SCID 小鼠 BL 异种移植瘤的生长，抑制率为 73.13%。我们的数据表明，TP 通过增加 SIRT3 的表达和激活 SIRT3/GSK-3β/Bax 通路，在 BL 中触发线粒体凋亡途径。这项研究表明，TP 是一种潜在的抗 BL 中草药。
