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Effects on Energy Metabolism of Two Guanidine Molecules, (Boc)2 -Creatine and Metformin.
Journal of Cellular Biochemistry ( IF 3.0 ) Pub Date : 2017 Jan 27 , DOI: 10.1002/jcb.25914
Patrizia Garbati 1 , Silvia Ravera 2 , Sonia Scarfì 3 , Annalisa Salis 4 , Camillo Rosano 5 , Alessandro Poggi 6 , Gianluca Damonte 4, 7 , Enrico Millo 4, 7 , Maurizio Balestrino 1
Affiliation  

Several enzymes are involved in the energy production, becoming a possible target for new anti-cancer drugs. In this paper, we used biochemical and in silico studies to evaluate the effects of two guanidine molecules, (Boc)2 -creatine and metformin, on creatine kinase, an enzyme involved in the regulation of intracellular energy levels. Our results show that both drugs inhibit creatine kinase activity; however, (Boc)2 -creatine displays a competitive inhibition, while metformin acts with a non-competitive mechanism. Moreover, (Boc)2 -creatine is able to inhibit the activity of hexokinase with a non-competitive mechanism. Considering that creatine kinase and hexokinase are involved in energy metabolism, we evaluated the effects of (Boc)2 -creatine and metformin on the ATP/AMP ratio and on cellular proliferation in healthy fibroblasts, human breast cancer cells (MDA-MB-468), a human neuroblastoma cell line (SH-SY5Y), a human Hodgkin lymphoma cell line (KMH2). We found that healthy fibroblasts were only partially affected by (Boc)2 -creatine, while both ATP/AMP ratio and viability of the three cancer cell lines were significantly decreased. By inhibiting both creatine kinase and hexokinase, (Boc)2 -creatine appears as a promising new agent in anticancer treatment. Further research is needed to understand what types of cancer cells are most suitable to treatment by this new compound. J. Cell. Biochem. 9999: 1-12, 2017. (c) 2017 Wiley Periodicals, Inc.

中文翻译:

对两个胍分子(Boc)2-肌酸和二甲双胍能量代谢的影响。

几种酶参与能量产生,成为新的抗癌药物的可能靶标。在本文中,我们使用生化和计算机模拟研究来评估两个胍分子(Boc)2-肌酸和二甲双胍对肌酸激酶的作用,肌酸激酶是一种参与细胞内能量水平调节的酶。我们的结果表明,两种药物均抑制肌酸激酶活性。但是,(Boc)2-肌酸具有竞争性抑制作用,而二甲双胍则具有非竞争性机制。此外,(Boc)2-肌酸能够以非竞争性机制抑制己糖激酶的活性。考虑到肌酸激酶和己糖激酶参与能量代谢,我们评估了(Boc)2-肌酸和二甲双胍对健康成纤维细胞中ATP / AMP比和细胞增殖的影响,人乳腺癌细胞(MDA-MB-468),人神经母细胞瘤细胞系(SH-SY5Y),人霍奇金淋巴瘤细胞系(KMH2)。我们发现健康的成纤维细胞仅部分受到(Boc)2-肌酸的影响,而这三种癌细胞系的ATP / AMP比和活力均显着降低。通过同时抑制肌酸激酶和己糖激酶,(Boc)2-肌酸在抗癌治疗中有望成为一种有希望的新药。需要进一步的研究来了解哪种类型的癌细胞最适合用这种新化合物治疗。J.细胞。生化。9999:1-12,2017.(c)2017威利期刊公司 而这三种癌细胞系的ATP / AMP比和活力均显着降低。通过同时抑制肌酸激酶和己糖激酶,(Boc)2-肌酸在抗癌治疗中作为有希望的新药出现。需要进一步的研究来了解哪种类型的癌细胞最适合用这种新化合物治疗。J.细胞。生化。9999:1-12,2017.(c)2017威利期刊公司 而这三种癌细胞系的ATP / AMP比和活力均显着降低。通过同时抑制肌酸激酶和己糖激酶,(Boc)2-肌酸在抗癌治疗中有望成为一种有希望的新药。需要进一步的研究来了解哪种类型的癌细胞最适合用这种新化合物治疗。J.细胞。生化。9999:1-12,2017.(c)2017威利期刊公司
更新日期:2017-01-31
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