Anticancer Effects of Sinocrassulosides VI/VII from Silene viscidula on HeLa Cells.

Anticancer Effects of Sinocrassulosides VI/VII from Silene viscidula on HeLa Cells.
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Silene viscidula 中的青果苷 VI/VII 对 HeLa 细胞的抗癌作用

DOI:
10.1155/2017/8240820
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发表时间:
2017
期刊:
Evidence-based complementary and alternative medicine : eCAM
影响因子:
--
通讯作者:
Fang J
Fang J
中科院分区:
其他
文献类型:
--
作者:
Chen H;Ma Q;Xu W;Li WM;Yuan DZ;Wu JM;Li YS;Fang J

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天然产品在化学预防和癌症治疗中正变得越来越重要。粘胶是一种传统的中草药,长期以来一直被用作抗炎和神经镇静剂。然而,粘性链球菌的抗癌活性仍不清楚。在本研究中,从粘菌中提取了16个化合物。其中,异构体化合物对HeLa细胞的抑制作用最强,IC50值为2.37 μM。机制研究发现,它们下调细胞周期蛋白D1的表达,降低视网膜母细胞瘤(Rb)的磷酸化,使细胞停滞于G1期。此外,皂苷VI/VII还可通过上调p16和β-半乳糖苷酶(β-GAL)染色而诱导衰老。我们的研究结果表明,华中皂苷VI/VII可能是一种新的治疗宫颈癌的潜在药物。此外,我们还研究了粘性链球菌中化学结构相似的三组构型异构体的构效关系。我们首先证明了与葡萄糖醛酸残基的羧基相连的酯链的长度可以影响其强大的细胞毒性。这一发现将为通过修饰从自然界植物中提取的成分来开发有效的抗癌化合物开辟新的途径。
Natural products are becoming increasingly important in chemoprevention and for cancer therapy. Silene viscidula (S. viscidula), a traditional Chinese herb, has long been used as an anti-inflammatory and neuroleptic agent. However, the anticancer activity of S. viscidula has remained unclear. In this study, 16 compounds were extracted from S. viscidula. Among those compounds, sinocrassulosides VI/VII, an inseparable isomer mixture, possess the strongest inhibitory activity on HeLa cells with the IC50 value of 2.37 μM. Mechanism studies found that sinocrassulosides VI/VII downregulated the expression of cyclin D1 and decreased retinoblastoma (Rb) phosphorylation, which arrested HeLa cells in the G1 phase. Also, sinocrassulosides VI/VII could induce senescence via the upregulation of p16 and a significant increase of β-galactosidase (β-gal) staining. Our results suggest that sinocrassulosides VI/VII may be a new therapeutic potential agent for cervical cancer. In addition, we explored the structure-activity relationships of three groups of the configurational isomer with similar chemical structure from S. viscidula. We first demonstrated that the length of the ester chains linked to the carboxyl group of the glucuronic acid residue could affect the potent cytotoxicity. This finding will open new avenues for developing effective anticancer compounds by modifying the components derived from plants in nature.
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