Key Laboratory of Ethnomedicine of Ministry of Education, Center on Translational Neuroscience, School of Pharmacy, Minzu University of China, Beijing, 100081, PR China.
Key Laboratory of Ethnomedicine of Ministry of Education, Center on Translational Neuroscience, School of Pharmacy, Minzu University of China, Beijing, 100081, PR China.
J Ethnopharmacol. 2021 Jun 12;273:114017. doi: 10.1016/j.jep.2021.114017. Epub 2021 Mar 11.
Gynostemma pentaphyllum (Thunb.) Makino, a traditional medicine in China, has been widely used for the treatment of various diseases. Gypenoside LI (Gyp LI) is a major constituent from steamed G. pentaphyllum. Previous studies have shown that gypnenoside LI possess inhibitory effect on the growth of many cancer cells. However, its pharmacological effect in breast cancer and the mechanism have not been reported yet.
To investigate the anti-breast cancer activity of gypenoside LI and underlying mechanisms of gypenoside LI in MDA-MB-231 and MCF-7 cells.
MATERIAL/METHODS: The cytotoxicity of gypenoside LI was determined by MTT, colony-formation and three-dimensional spheroid assay. The migration, cell apoptosis and the cell cycle were investigated through cell morphology observation, flow cytometry analysis and key proteins detection. The anticancer mechanisms of gypenoside LI were detected by RNA sequencing (RNA-seq) and Gene Set Enrichment Analysis (GSEA) transcriptome analysis.
Gypenoside LI inhibited cell proliferation, migration, induced cell apoptosis and cell cycle arrest. Gypenoside LI arrested cell cycle at G0/G1 phase by regulating E2F1. It also inhibited tumor proliferation by regulating the expression of ERCC6L. Interestingly, we found that E2F1 siRNA also down-regulated the expression of ERCC6L. Gypenoside LI showed potential anti-breast cancer cells activity, especially on triple-negative breast cancer cells.
These data indicate that gypenoside LI could inhibit human breast cancer cells through inhibiting proliferation and migration, inducing apoptosis, arresting cell cycle at G0/G1 phase by regulating E2F1. It could be used as potential multi-target chemopreventive agents for cancer.
绞股蓝（Thunb.）Makino，中国传统医学中的一种药物，已被广泛用于治疗各种疾病。绞股蓝皂苷 LI（Gyp LI）是蒸制绞股蓝的主要成分之一。先前的研究表明，绞股蓝皂苷 LI 对许多癌细胞的生长具有抑制作用。然而，其在乳腺癌中的药理作用及其机制尚未报道。
研究绞股蓝皂苷 LI 的抗乳腺癌活性及其在 MDA-MB-231 和 MCF-7 细胞中的作用机制。
材料/方法：通过 MTT、集落形成和三维球体形成实验测定绞股蓝皂苷 LI 的细胞毒性。通过细胞形态观察、流式细胞术分析和关键蛋白检测研究迁移、细胞凋亡和细胞周期。通过 RNA 测序（RNA-seq）和基因集富集分析（GSEA）转录组分析检测绞股蓝皂苷 LI 的抗癌机制。
绞股蓝皂苷 LI 抑制细胞增殖、迁移，诱导细胞凋亡和细胞周期停滞。绞股蓝皂苷 LI 通过调节 E2F1 将细胞周期阻滞在 G0/G1 期。它还通过调节 ERCC6L 的表达抑制肿瘤增殖。有趣的是，我们发现 E2F1 siRNA 也下调了 ERCC6L 的表达。绞股蓝皂苷 LI 表现出潜在的抗乳腺癌细胞活性，尤其是对三阴性乳腺癌细胞。
这些数据表明，绞股蓝皂苷 LI 可通过抑制增殖和迁移、诱导细胞凋亡、通过调节 E2F1 将细胞周期阻滞在 G0/G1 期来抑制人乳腺癌细胞。它可以作为癌症的潜在多靶标化学预防剂。
