Exploring Glyoxalase 1 Expression in Prostate Cancer Tissues:Targeting the Enzyme by Ethyl Pyruvate Defangs Some Malignancy-Associated Properties
Exploring Glyoxalase 1 Expression in Prostate Cancer Tissues:Targeting the Enzyme by Ethyl Pyruvate Defangs Some Malignancy-Associated Properties
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DOI：
10.1002/pros.22728
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发表时间：
2014-01-01
期刊：
影响因子：
2.8
通讯作者：
Birkenmeier, Gerd
中科院分区：
文献类型：
--
作者：
Baunacke, Martin;Horn, Lars-Christian;Birkenmeier, Gerd
研究背景谷胱甘肽酶（glycoproteinase，GLO）1是正常细胞和肿瘤细胞糖酵解途径中普遍存在的解毒系统的一部分。目的探讨GLO 1在前列腺癌中的作用，我们评估和靶向前列腺癌组织和细胞系中GLO 1的表达，并分析其与分级系统和肿瘤生长指数的相关性。（P=0.002）/核（P=0.006）GLO 1水平。Ki-67增殖标志物与胞浆GLO 1表达呈正相关（P=0.006）。此外，在蛋白质和mRNA水平上，与雄激素非依赖性Du-145和PC-3前列腺细胞系以及乳腺癌细胞MCF-7相比，在雄激素敏感性LNCaP中检测到最高的GLO 1水平。用丙酮酸乙酯处理癌细胞被发现可以解除癌细胞的一些恶性相关特性，包括增殖、侵袭和非锚定依赖性生长。体外实验结果表明，当细胞被生长刺激因子（如胎牛血清、双氢睾酮、肿瘤生长因子-1和leptin）代谢激活时，丙酮酸乙酯的作用增强。结论前列腺癌组织中GLO 1的表达水平与前列腺癌的病理分级和增殖率呈正相关，可能是前列腺癌发生发展的危险因素。此外，我们的数据表明，GLO 1的抑制剂可能是有用的，以减缓癌细胞的生长，通过一种新的治疗方法，我们可以称之为诱导代谢灾难。前列腺74：48-60，2014年。(c)2013 Wiley Periodicals，Inc.
BACKGROUNDThe glyoxalase (GLO)1 is part of a ubiquitous detoxification system in the glycolytic pathway of normal and tumor cells. It protects against cellular damage caused by cytotoxic metabolites.METHODSAiming at exploring the role of GLO1 in prostate cancer, we evaluated and targeted the expression of GLO1 in prostate cancer tissues and cell lines and analyzed its correlation with grading systems and tumor growth indices.RESULTSImmunohistochemical studies on 37 prostate cancer specimens revealed a positive correlation between Helpap-grading and the cytoplasmic (P=0.002)/nuclear (P=0.006) GLO1 level. A positive correlation between Ki-67 proliferation marker and the cytoplasmic GLO1 (P=0.006) was evident. Furthermore, the highest GLO1 level was detected in the androgen-sensitive LNCaP compared to the androgen-independent Du-145 and PC-3 prostate cell lines and the breast cancer cell MCF-7, both at protein and mRNA level. Treating cancer cells with ethyl pyruvate was found to defang some malignancy-associated properties of cancer cells including proliferation, invasion and anchorage-independent growth. In vitro results revealed that the potency of ethyl pyruvate is increased when cells are metabolically activated by growth stimulators, for example, by fetal calf serum, dihydrotestosterone, tumor growth factor-1 and leptin.CONCLUSIONSThe positive correlation of GLO1 expression level in prostate cancer tissues with the pathological grade and proliferation rate may assign GLO1 as a risk factor for prostate cancer development and progression. Furthermore, our data indicate that inhibitors of GLO1 might be useful to decelerate the cancer cell growth by a novel therapeutic approach that we may call induced metabolic catastrophe. Prostate 74:48-60, 2014. (c) 2013 Wiley Periodicals, Inc.