Trans-4-lodo,4′-boranyl-chalcone induces antitumor activity against malignant glioma cell lines in vitro and in vivo
Trans-4-lodo,4′-boranyl-chalcone induces antitumor activity against malignant glioma cell lines in vitro and in vivo
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DOI：
10.1007/s11060-007-9395-2
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发表时间：
2007-05
影响因子：
3.9
通讯作者：
T. Sasayama;Kazuhiro Tanaka;K. Mizukawa;A. Kawamura;T. Kondoh;K. Hosoda;E. Kohmura
中科院分区：
文献类型：
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作者：
T. Sasayama;Kazuhiro Tanaka;K. Mizukawa;A. Kawamura;T. Kondoh;K. Hosoda;E. Kohmura
查尔酮类化合物被认为是类黄酮类化合物的前体，已被鉴定为具有抗肿瘤活性的有趣化合物。与正常乳腺细胞相比，硼-查尔酮衍生物对乳腺癌细胞的毒性更大。在这里，我们研究了反式-4-LoDo，4‘-硼酰查尔酮(TLBC)，它是一种硼-查尔酮衍生物，在几种胶质瘤细胞系中的抗肿瘤活性。TLBC对不同胶质瘤细胞株的抑制作用呈剂量依赖性，抑制浓度50%值在μM范围内(5.5~2 5.5μM)。流式细胞仪和免疫印迹分析表明，TLBC诱导的细胞凋亡不依赖于肿瘤抑制基因P53的改变。这种细胞毒作用是通过caspase依赖的方式实现的。此外，TLBC还降低了几种细胞系中抗凋亡的Bcl2和/或BclXL蛋白的水平。为了检测TLBC在体内的抗肿瘤作用，我们使用了恶性胶质瘤异种移植模型。结果表明，TLBC 20 mg/kg组小鼠平均肿瘤体积较对照组缩小43.9%(P<；P<0.01)。免疫组织化学和免疫印迹分析显示，与对照组相比，注射TLBC 20 mg/kg组肿瘤组织中Bcl2蛋白表达水平降低，Bax蛋白表达水平略有升高。因此，我们认为TLBC可能是一种潜在的人脑胶质瘤化疗药物。
Chalcones are considered the precursors of flavonoids and have been identified as interesting compounds with antitumor properties. Boronic-chalcone derivatives are more toxic to breast cancer cells compared to normal breast cells. Here, we studied the antitumor activities of trans-4-lodo,4′-boranyl-chalcone (TLBC), which is a boronic-chalcone derivative, in several glioma cell lines. TLBC showed a dose-dependent inhibition with inhibitory concentration 50% value in the μM range (5.5–25.5 μM) in various glioma cell lines. Flow cytometric and western blot assay demonstrated that TLBC induced apoptosis independent of changes to the tumor suppressor p53. This cytotoxic effect was the caspase-dependent manner. Also, TLBC lowered levels of anti-apoptotic Bcl-2 and/or Bcl-XLprotein in several of the cell lines. To examine the antitumor effect of TLBCin vivo, we used a malignant glioma xenograft model. This result showed that in the mice treated with TLBC at 20 mg/kg, mean tumor volume was reduced by 43.9% (P< 0.01) in comparison with the control group. Immunohistochemical and western blot analysis showed that Bcl-2 protein levels were decreased and Bax protein levels were slightly increased in the tumors injected with 20 mg/kg TLBC compared with the control tumors. Therefore, we conclude that TLBC may be a potential chemotherapeutic agent for human glioma.