间质细胞
癌症研究
子宫内膜间质肉瘤
细胞周期
细胞周期检查点
PI3K/AKT/mTOR通路
生物
细胞凋亡
伏立诺他
细胞生长
程序性细胞死亡
组蛋白脱乙酰酶抑制剂
间充质干细胞
化学
组蛋白脱乙酰基酶
细胞生物学
组蛋白
信号转导
基因
遗传学
生物化学
作者
Andelko Hrzenjak,Marie-Luise Kremser,Bettina Strohmeier,Farid Moinfar,Kurt Zatloukal,Helmut Denk
摘要
Endometrial stromal sarcomas are rare and molecular mechanisms involved in their pathogenesis are poorly understood. Covalent modifications of histone proteins, in particular de/acetylation of lysine residues, play an important role in the regulation of gene transcription in normal and neoplastic cells, but there are only limited data about these processes in solid mesenchymal tumours. We treated endometrial stromal sarcoma cells (ESS-1) and non-malignant human endometrial stromal cells (HESCs) with suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor. SAHA was able to mediate the cell cycle and expression of genes related to the malignant phenotype of endometrial stromal tumours, eg p21(WAF1) and HDAC7. SAHA led to dose-dependent differentiation and death of ESS-1 cells but not of HESCs. Exposure of HESCs to SAHA resulted only in slightly decreased cell proliferation. SAHA also increased the p21(WAF1) expression and caused significant changes in the cell cycle by inhibiting the G1/S transition in ESS-1 cells. Recovery experiments indicated that these changes became irreversible when the tumour cells were treated with SAHA for longer than 24 h. In our experimental system, not apoptotic but autophagic processes were responsible for the cell death. Monodansyl cadaverine accumulation in treated ESS-1 cells and decreased expression of the mTOR and phospho-S6 ribosomal protein (S6rp) additionally supported this observation. Taken together, our study indicates that HDACs might be considered as potential drug targets in the therapy of stromal sarcomas and that SAHA might be a promising therapeutic agent for endometrial stromal sarcoma.
科研通智能强力驱动
Strongly Powered by AbleSci AI