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Serotonin Analogues as Inhibitors of Breast Cancer Cell Growth
ACS Medicinal Chemistry Letters ( IF 4.2 ) Pub Date : 2017-09-19 00:00:00 , DOI: 10.1021/acsmedchemlett.7b00282
Jiney Jose 1, 2 , Clint D. J. Tavares 1, 3 , Nancy D. Ebelt 1, 3 , Alessia Lodi 4 , Ramakrishna Edupuganti 1, 2 , Xuemei Xie 5, 6 , Ashwini K. Devkota 1, 3 , Tamer S. Kaoud 1 , Carla L. Van Den Berg 3, 7 , Eric V. Anslyn 2 , Stefano Tiziani 4 , Chandra Bartholomeusz 5, 6 , Kevin N. Dalby 1, 3
Affiliation  

Serotonin (5-hydroxytryptamine, 5-HT) is a critical local regulator of epithelial homeostasis in the breast and exerts its actions through a number of receptors. Dysregulation of serotonin signaling is reported to contribute to breast cancer pathophysiology by enhancing cell proliferation and promoting resistance to apoptosis. Preliminary analyses indicated that the potent 5-HT1B/1D serotonin receptor agonist 5-nonyloxytryptamine (5-NT), a triptan-like molecule, induced cell death in breast cancer cell lines. Thus, we synthesized a series of novel alkyloxytryptamine analogues, several of which decreased the viability of various human cancer cell lines. Proteomic and metabolomic analyses showed that compounds 6 and 10 induced apoptosis and interfered with signaling pathways that regulate protein translation and survival, such as the Akt/mTOR pathway, in triple-negative breast cancer cells.

中文翻译:

5-羟色胺类似物作为乳腺癌细胞生长的抑制剂。

5-羟色胺(5-羟色胺,5-HT)是乳腺上皮稳态的关键局部调节剂,可通过多种受体发挥作用。据报道,5-羟色胺信号转导的失调通过增强细胞增殖并增强对凋亡的抵抗力而有助于乳腺癌的病理生理。初步分析表明,强效的5-HT1B / 1D血清素受体激动剂5-壬基氧基色胺(5-NT)(一种曲普坦样分子)可诱导乳腺癌细胞系中的细胞死亡。因此,我们合成了一系列新颖的烷氧基色胺类似物,其中一些降低了各种人类癌细胞系的生存能力。蛋白质组学和代谢组学分析表明化合物610 在三阴性乳腺癌细胞中诱导凋亡,并干扰调节蛋白质翻译和存活的信号传导途径,例如Akt / mTOR途径。
更新日期:2017-09-19
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