Thiocoraline activates the Notch pathway in carcinoids and reduces tumor progression in vivo.
Thiocoraline activates the Notch pathway in carcinoids and reduces tumor progression in vivo.
复制标题
Thiocoraline 激活类癌中的 Notch 通路并减少体内肿瘤进展。
DOI：
10.1038/cgt.2014.57
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发表时间：
2014
影响因子：
6.4
通讯作者：
Jaskula-Sztul,R
中科院分区：
文献类型：
--
作者：
Wyche,TP;Dammalapati,A;Cho,H;Harrison,AD;Kwon,GS;Chen,H;Bugni,TS;Jaskula-Sztul,R
Carcinoids are slow-growing neuroendocrine tumors (NETs) that are characterized by hormone overproduction; surgery is currently the only option for treatment. Activation of the Notch pathway has previously been shown to have a role in tumor suppression in NETs. The marine-derived thiodepsipeptide thiocoraline was investigated in vitro in two carcinoid cell lines (BON and H727). Carcinoid cells treated with nanomolar concentrations of thiocoraline resulted in a decrease in cell proliferation and an alteration of malignant phenotype evidenced by decrease of NET markers, achaete-scute complex like-1, chromogranin A and neurospecific enolase. Western blotting analysis demonstrated the activation of Notch1 on the protein level in BON cells. Additionally, thiocoraline activated downstream Notch targets HES1, HES5 and HEY2. Thiocoraline effectively suppressed carcinoid cell growth by promoting cell cycle arrest in BON and H727 cells. An in vivo study demonstrated that thiocoraline, formulated with polymeric micelles, slowed carcinoid tumor progression. Thus the therapeutic potential of thiocoraline, which induced activation of the Notch pathway, in carcinoid tumors was demonstrated.
