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迷迭香酸是中药覆盆子的活性成分,通过线粒体途径诱导 SGC-7901 和 HepG2 细胞凋亡,发挥抗肿瘤作用。

Rosmarinic acid, the active component of Rubi Fructus, induces apoptosis of SGC-7901 and HepG2 cells through mitochondrial pathway and exerts anti-tumor effect.

机构信息

College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 311402, China.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2023 Dec;396(12):3743-3755. doi: 10.1007/s00210-023-02552-z. Epub 2023 Jun 20.

Abstract

Rosmarinic acid (RA) is a well-known phenolic acid widely present in over 160 species of herbal plants and known to exhibit anti-tumor effects on breast, prostate, and colon cancers in vitro. However, its effect and mechanism in gastric cancer and liver cancer are unclear. Moreover, there is no RA report yet in the chemical constituents of Rubi Fructus (RF). In this study, RA was isolated from RF for the first time, and the effect and mechanism of RA on gastric and liver cancers were evaluated using SGC-7901 and HepG2 cells models. The cells were treated with different concentrations of RA (50, 75, and 100 μg/mL) for 48 h, and the effect of RA on cell proliferation was evaluated by the CCK-8 assay. The effect of RA on cell morphology and mobility was observed by inverted fluorescence microscopy, cell apoptosis and cell cycle were determined by flow cytometry, and the expression of apoptosis-related proteins cytochrome C, cleaved caspase-3, Bax, and Bcl-2 was detected by western blotting. The results revealed that, with an increase in the RA concentration, the cell viability, mobility, and Bcl-2 expression decreased, while the apoptosis rate, Bax, cytochrome C, and cleaved caspase-3 expression increased, and SGC-7901 and HepG2 cells could be induced to arrest their cell cycle in the G0/G1 and S phases, respectively. These results together indicate that RA can induce apoptosis of SGC-7901 and HepG2 cells through the mitochondrial pathway. Thus, this study supplements the material basis of the anti-tumor activity of RF and provides an insight into the potential mechanism of RA-inducing apoptosis of gastric cancer SGC-7901 cells and liver cancer HepG2 cells, thereby facilitating further developmental studies on and the utilization of the anti-tumor activity of RF.

摘要

迷迭香酸(RA)是一种广泛存在于 160 多种草药植物中的知名酚酸,已知其在体外对乳腺癌、前列腺癌和结肠癌具有抗肿瘤作用。然而,其在胃癌和肝癌中的作用和机制尚不清楚。此外,在覆盆子的化学成分中尚未有关于迷迭香酸的报道。在这项研究中,首次从覆盆子中分离出迷迭香酸,并通过 SGC-7901 和 HepG2 细胞模型评估 RA 对胃癌和肝癌的作用和机制。将细胞用不同浓度的 RA(50、75 和 100μg/ml)处理 48 小时,通过 CCK-8 测定评估 RA 对细胞增殖的影响。通过倒置荧光显微镜观察 RA 对细胞形态和迁移的影响,通过流式细胞术测定细胞凋亡和细胞周期,通过 Western blot 检测凋亡相关蛋白细胞色素 C、裂解的 caspase-3、Bax 和 Bcl-2 的表达。结果表明,随着 RA 浓度的增加,细胞活力、迁移能力和 Bcl-2 表达降低,而凋亡率、Bax、细胞色素 C 和裂解的 caspase-3 表达增加,SGC-7901 和 HepG2 细胞分别被诱导其细胞周期停滞在 G0/G1 和 S 期。这些结果表明,RA 可以通过线粒体途径诱导 SGC-7901 和 HepG2 细胞凋亡。因此,本研究补充了覆盆子抗肿瘤活性的物质基础,并为迷迭香酸诱导胃癌 SGC-7901 细胞和肝癌 HepG2 细胞凋亡的潜在机制提供了新的认识,从而促进了对覆盆子抗肿瘤活性的进一步开发研究和利用。

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