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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >A sesquiterpenelactone from Inula britannica induces anti-tumor effects dependent on Bcl-2 phosphorylation.
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A sesquiterpenelactone from Inula britannica induces anti-tumor effects dependent on Bcl-2 phosphorylation.

机译：来自大花菊的倍半萜内酯诱导依赖于Bcl-2磷酸化的抗肿瘤作用。

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BACKGROUND: The over-expression of the anti-apoptotic protein Bcl-2 in cancer is associated with resistance to chemotherapeutic drugs. The phosphorylation of Bcl-2 is one mechanism by which anti-microtubule agents, such as paclitaxel or docetaxel, may inactivate Bcl-2. Although initially active in clinical studies, current anti-microtubule agents are only temporarily effective and the discovery of new agents is warranted. MATERIALS AND METHODS: We isolated and identified two known sesquiterpenelactones, O, O-diacetylbritannilactone (OODABL) and O-acetylbritaanilactone (OABL) from the flowers of the medicinal plant Inula britannica and studied their mechanism of anti-tumor effects. To determine the biological significance of Bcl-2 phosphorylation, we used a baby rat kidney (BRK-p53) cell line that was transformed with EIA and a temperature-sensitive mutant p53. The BRK-p53 cell line was transfected with either a vector with wild type Bcl-2 or a vector in which Bcl-2 had mutations in the paclitaxel phosphorylation sites (pcDNA3.1 V5/His Bcl-2 S70, 87A). RESULTS: OODABL and OABL induced phosphorylation of Bcl-2 in breast, ovary and prostate cancer cell lines and induced G2/M cell cycle arrest. Using the BRK cells with mutant Bcl-2 (BRK-Bcl-2-mt) and control (BRK-Bcl-2-wt), we found that OODABL induced phosphorylation of Bcl-2 at sites similar to paclitaxel. Phosphorylation of Bcl-2 was important for OODABL-induced cytotoxicity, since the abrogation of phosphorylation in BRK-Bcl-2-mt cells decreased OODABL-induced cytotoxicity. CONCLUSION: We concluded that OODABL is cytotoxic in multiple tumor cell lines, and the cytotoxicity is dependent, at least in part, on the phosphorylation of Bcl-2.
机译：背景：抗凋亡蛋白Bcl-2在癌症中的过度表达与对化疗药物的耐药性有关。 Bcl-2的磷酸化是一种机制，通过这种机制，抗微管药（例如紫杉醇或多西紫杉醇）可能会使Bcl-2失活。尽管最初在临床研究中很活跃，但是目前的抗微管药物只是暂时有效的，因此有必要发现新的药物。材料与方法：我们从药用植物大叶​​菊（Inula britannica）的花中分离并鉴定出两种已知的倍半萜内酯，O，O-二乙酰基溴内酯（OODABL）和O-乙酰基乙酰苯内酯（OABL），并研究了它们的抗肿瘤作用机理。为了确定Bcl-2磷酸化的生物学意义，我们使用了用EIA和温度敏感型突变体p53转化的大鼠肾脏（BRK-p53）细胞系。用具有野生型Bcl-2的载体或其中Bcl-2在紫杉醇磷酸化位点具有突变的载体（pcDNA3.1 V5 / His Bcl-2 S70，87A）转染BRK-p53细胞系。结果：OODABL和OABL诱导乳腺癌，卵巢癌和前列腺癌细胞系中Bcl-2的磷酸化，并诱导G2 / M细胞周期阻滞。使用具有突变Bcl-2（BRK-Bcl-2-mt）和对照（BRK-Bcl-2-wt）的BRK细胞，我们发现OODABL在与紫杉醇相似的位点诱导Bcl-2的磷酸化。 Bcl-2的磷酸化对于OODABL诱导的细胞毒性很重要，因为BRK-Bcl-2-mt细胞中磷酸化的消除可以降低OODABL诱导的细胞毒性。结论：我们得出结论，OODABL在多种肿瘤细胞系中具有细胞毒性，并且细胞毒性至少部分取决于Bcl-2的磷酸化。

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