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绞股蓝皂苷H,一种新型达玛烷型三萜,可诱导前列腺癌细胞的细胞周期停滞和凋亡。

Gypensapogenin H, a novel dammarane-type triterpene induces cell cycle arrest and apoptosis on prostate cancer cells.

作者信息

Zhang Xiao-Shu, Zhao Chen, Tang Wei-zhuo, Wu Xiao-jun, Zhao Yu-Qing

机构信息

School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China; Key Laboratory of Structure-Based Drug Design and Discovery, Shenyang Pharmaceutical University, Ministry of Education, Shenyang 110016, People's Republic of China.

Key Laboratory of Structure-Based Drug Design and Discovery, Shenyang Pharmaceutical University, Ministry of Education, Shenyang 110016, People's Republic of China; Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.

出版信息

Steroids. 2015 Dec;104:276-83. doi: 10.1016/j.steroids.2015.10.014. Epub 2015 Oct 26.

Abstract

Gypensapogenin H (GH) is a novel dammarane-type triterpenes obtained from hydrolyzate of total saponins from Gynostemma pentaphyllum and its anti-tumor activity has been studied in previous work. In this study, we report the effects of this compound on human prostate cancer cells (DU145 and 22RV-1). It significantly inhibited proliferation, decreased survival, led to G1 cell cycle arrest and induced apoptosis in both cell lines, while having lesser effect on the growth of normal human gastric mucosa cells (GES-1), embryonic kidney cells (HEK293) and lung fibroblast cells (MRC5). Consistent with these phenotypes, we observed decreased expression of the cell cycle-related proteins cyclinD1, and CDK4, and increased expression of p21 in GH-treated cells. Besides, the anti-apoptotic Bcl-2 protein decreased in a dose-dependent manner, while Bax, cleaved caspase-3 and -9 increased upon GH treatment. Taken together, these results indicated GH exerted promising anticancer activity, and may represent a potential agent for the treatment of prostate cancer.

摘要

绞股蓝皂苷元H(GH)是从绞股蓝总皂苷水解产物中获得的一种新型达玛烷型三萜,其抗肿瘤活性已在先前的研究中有所探讨。在本研究中,我们报告了该化合物对人前列腺癌细胞(DU145和22RV-1)的影响。它显著抑制了这两种细胞系的增殖,降低了细胞存活率,导致G1期细胞周期阻滞并诱导凋亡,而对正常人胃黏膜细胞(GES-1)、胚胎肾细胞(HEK293)和肺成纤维细胞(MRC5)的生长影响较小。与这些表型一致,我们观察到在经GH处理的细胞中,细胞周期相关蛋白细胞周期蛋白D1和细胞周期蛋白依赖性激酶4的表达降低,而p21的表达增加。此外,抗凋亡蛋白Bcl-2以剂量依赖性方式减少,而Bax、裂解的半胱天冬酶-3和-9在GH处理后增加。综上所述,这些结果表明GH具有良好的抗癌活性,可能是一种治疗前列腺癌的潜在药物。

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