Spermine oxidase (SMO) activity in breast tumor tissues and biochemical analysis of the anticancer spermine analogues BENSpm and CPENSpm.
Spermine oxidase (SMO) activity in breast tumor tissues and biochemical analysis of the anticancer spermine analogues BENSpm and CPENSpm.
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乳腺肿瘤组织中的精胺氧化酶 (SMO) 活性以及抗癌精胺类似物 BENSpm 和 CPENSpm 的生化分析。
DOI：
10.1186/1471-2407-10-555
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发表时间：
2010-10-14
期刊：
影响因子：
3.8
通讯作者：
Mariottini P
中科院分区：
文献类型：
--
作者：
Cervelli M;Bellavia G;Fratini E;Amendola R;Polticelli F;Barba M;Federico R;Signore F;Gucciardo G;Grillo R;Woster PM;Casero RA Jr;Mariottini P
多胺代谢在细胞死亡和增殖中起关键作用，是乳腺癌干预的潜在目标。本研究探讨精胺氧化酶（SMO）在BC中的表达及其预后意义。对用于抗癌治疗的Spm类似物BENSpm和CPENSpm也进行了生化分析，以测试其在重组SMO酶上的硅和体外特性。分析BC组织样本的SMO转录物水平和SMO活性。使用学生t检验来评估t和NT样本中观察到的值差异的显著性。通过体外实验检测SMO酶形成的BENSpm和CPENSpm复合物的结构建模分析和抑制活性。与NT样品相比，BC样品中SMO mRNA的表达水平和SMO酶活性均显著降低。与SMO形成的BENSpm和CPENSpm配合物的模型及其抑制性能表明，两者都是良好的抑制剂。本研究表明SMO的低表达是BC的阴性标志物。SMO诱导是一个重要的化疗靶点。BENSpm和CPENSpm是有效的SMO抑制剂。这些类似物所显示的抑制特性可以解释它们在临床试验I期和II期的不良积极结果。
Polyamine metabolism has a critical role in cell death and proliferation representing a potential target for intervention in breast cancer (BC). This study investigates the expression of spermine oxidase (SMO) and its prognostic significance in BC. Biochemical analysis of Spm analogues BENSpm and CPENSpm, utilized in anticancer therapy, was also carried out to test their property in silico and in vitro on the recombinant SMO enzyme. BC tissue samples were analyzed for SMO transcript level and SMO activity. Student's t test was applied to evaluate the significance of the differences in value observed in T and NT samples. The structure modeling analysis of BENSpm and CPENSpm complexes formed with the SMO enzyme and their inhibitory activity, assayed by in vitro experiments, were examined. Both the expression level of SMO mRNA and SMO enzyme activity were significantly lower in BC samples compared to NT samples. The modeling of BENSpm and CPENSpm complexes formed with SMO and their inhibition properties showed that both were good inhibitors. This study shows that underexpression of SMO is a negative marker in BC. The SMO induction is a remarkable chemotherapeutical target. The BENSpm and CPENSpm are efficient SMO inhibitors. The inhibition properties shown by these analogues could explain their poor positive outcomes in Phases I and II of clinical trials.
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影响因子：
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作者：
Hiramatsu, K;Takahashi, K;Kawakita, M
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影响因子：
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通讯作者：
BRADFORD, MM