Hoffmann Dorit, Rentsch Andreas, Vighi Eleonora, Bertolotti Evelina, Comitato Antonella, Schwede Frank, Genieser Hans-Gottfried, Marigo Valeria
Università degli Studi di Modena e Reggio Emilia, Via Campi 287, 41125 Modena, Italy.
BIOLOG Life Science Institute Forschungslabor und Biochemica-Vertrieb GmbH, Flughafendamm 9a, 28199 Bremen, Germany.
Eur J Med Chem. 2017 Dec 1;141:61-72. doi: 10.1016/j.ejmech.2017.09.053. Epub 2017 Sep 27.
Activation of the cGMP-dependent protein kinase G (PKG) can inhibit growth and/or induce apoptosis in colon cancer. In this study we evaluated the effects on cell viability, cell death and proliferation of novel dimeric cGMP analogues, compared to a monomeric compound. Three colon cancer cell lines, which only express isoform 2 of PKG, were treated with these novel cGMP analogues and responded with increased PKG activity. cGMP analogues reduced cell viability in the three cell lines and this was due to a cytostatic rather than cytotoxic effect. These findings suggest that activation of PKG2 can be a therapeutic target in the treatment of colon cancer and, most importantly, that dimeric cGMP analogues can further improve the beneficial effects previously observed with monomeric cGMP analogues.
环磷酸鸟苷（cGMP）依赖性蛋白激酶G（PKG）的激活可抑制结肠癌生长和/或诱导其凋亡。在本研究中，我们评估了新型二聚体cGMP类似物与单体化合物相比对细胞活力、细胞死亡和增殖的影响。用这些新型cGMP类似物处理仅表达PKG同工型2的三种结肠癌细胞系，PKG活性增加。cGMP类似物降低了这三种细胞系的细胞活力，这是由于其细胞生长抑制作用而非细胞毒性作用。这些发现表明，PKG2的激活可能是结肠癌治疗的一个治疗靶点，最重要的是，二聚体cGMP类似物可进一步增强先前观察到的单体cGMP类似物的有益效果。
