Chen Hang, Ma Qian, Xu Wei, Li Wan-Ming, Yuan De-Zheng, Wu Jia-Mei, Li Yu-Shan, Fang Jin
Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China.
School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Wenhua Road 103, Shenhe District, Shenyang 110016, China.
Evid Based Complement Alternat Med. 2017;2017:8240820. doi: 10.1155/2017/8240820. Epub 2017 Jul 9.
Natural products are becoming increasingly important in chemoprevention and for cancer therapy. , a traditional Chinese herb, has long been used as an anti-inflammatory and neuroleptic agent. However, the anticancer activity of has remained unclear. In this study, 16 compounds were extracted from . Among those compounds, sinocrassulosides VI/VII, an inseparable isomer mixture, possess the strongest inhibitory activity on HeLa cells with the IC value of 2.37 M. 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 -galactosidase (-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 . 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.
天然产物在化学预防和癌症治疗中变得越来越重要。[具体草药名称]，一种传统的中国草药，长期以来一直被用作抗炎和抗精神病药物。然而，[该草药名称]的抗癌活性仍不清楚。在本研究中，从[该草药名称]中提取了16种化合物。在这些化合物中，中华景天苷VI/VII，一种不可分离的异构体混合物，对HeLa细胞具有最强的抑制活性，IC值为2.37μM。机制研究发现，中华景天苷VI/VII下调细胞周期蛋白D1的表达并降低视网膜母细胞瘤（Rb）的磷酸化，从而使HeLa细胞停滞在G1期。此外，中华景天苷VI/VII可通过上调p16和显著增加β-半乳糖苷酶（β-gal）染色诱导衰老。我们的结果表明，中华景天苷VI/VII可能是一种新的宫颈癌治疗潜在药物。此外，我们探索了从[该草药名称]中三组具有相似化学结构的构型异构体的构效关系。我们首次证明，与葡萄糖醛酸残基羧基相连的酯链长度会影响强大的细胞毒性。这一发现将为通过修饰天然植物衍生成分开发有效的抗癌化合物开辟新途径。
