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- 衍生的羊毛甾烷三萜通过 AKT/PI3K 和 MAPK 信号通路调节肿瘤细胞凋亡。

Regulation of Tumor Apoptosis of -Derived Lanostane Triterpenes by AKT/PI3K and MAPK Signaling Pathways .

机构信息

College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.

Department of Nutrition, Food Science and Packaging, San Jose State University, San Jose, CA 95192, USA.

出版信息

Nutrients. 2023 Oct 13;15(20):4360. doi: 10.3390/nu15204360.

Abstract

is traditionally used as both food and medicine. Triterpenoids in have a wide range of pharmacological activities, such as diuretic, sedative and tonic properties. In this study, the anti-tumor activities of poricoic acid A (PAA) and poricoic acid B (PAB), purified by high-speed counter-current chromatography, as well as their mechanisms and signaling pathways, were investigated using a HepG2 cell model. After treatment with PAA and PAB on HepG2 cells, the apoptosis was obviously increased ( < 0.05), and the cell cycle arrested in the G2/M phase. Studies showed that PAA and PAB can also inhibit the occurrence and development of tumor cells by stimulating the generation of ROS in tumor cells and inhibiting tumor migration and invasion. Combined Polymerase Chain Reaction and computer simulation of molecular docking were employed to explore the mechanism of tumor proliferation inhibition by PAA and PAB. By interfering with phosphatidylinositol-3-kinase/protein kinase B, Mitogen-activated protein kinases and p53 signaling pathways; and further affecting the expression of downstream caspases; matrix metalloproteinase family, cyclin-dependent kinase -cyclin, Intercellular adhesion molecules-1, Vascular Cell Adhesion Molecule-1 and Cyclooxygenase -2, may be responsible for their anti-tumor activity. Overall, the results suggested that PAA and PAB induced apoptosis, halted the cell cycle, and inhibited tumor migration and invasion through multi-pathway interactions, which may serve as a potential therapeutic agent against cancer.

摘要

灵芝传统上既被用作食物,也被用作药物。灵芝中的三萜类化合物具有广泛的药理活性,如利尿、镇静和滋补作用。在这项研究中,采用 HepG2 细胞模型,研究了高速逆流色谱法纯化的灵芝酸 A(PAA)和灵芝酸 B(PAB)的抗肿瘤活性及其机制和信号通路。用 PAA 和 PAB 处理 HepG2 细胞后,细胞凋亡明显增加(<0.05),细胞周期停滞在 G2/M 期。研究表明,PAA 和 PAB 还可以通过刺激肿瘤细胞中 ROS 的产生以及抑制肿瘤迁移和侵袭来抑制肿瘤细胞的发生和发展。采用聚合酶链反应和计算机模拟分子对接技术,探讨了 PAA 和 PAB 抑制肿瘤增殖的机制。通过干扰磷脂酰肌醇-3-激酶/蛋白激酶 B、丝裂原激活蛋白激酶和 p53 信号通路;并进一步影响下游半胱天冬酶、基质金属蛋白酶家族、细胞周期蛋白依赖性激酶-细胞周期蛋白、细胞间黏附分子-1、血管细胞黏附分子-1 和环氧化酶-2 的表达,可能是其抗肿瘤活性的原因。总的来说,这些结果表明,PAA 和 PAB 通过多途径相互作用诱导细胞凋亡、阻止细胞周期、抑制肿瘤迁移和侵袭,可能成为一种有潜力的抗癌治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45eb/10610537/d37f38916f06/nutrients-15-04360-g001.jpg

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