Amarogentin Induces Apoptosis of Liver Cancer Cells via Upregulation of p53 and Downregulation of Human Telomerase Reverse Transcriptase in Mice

Abstract

Background and Objective: Amarogentin has been reported to have a preventive effect on liver cancer via inducing cancer cell apoptosis. We attempted to elucidate the roles of p53-associated apoptosis pathways in the chemopreventive mechanism of amarogentin. The findings of this study will facilitate the development of a novel supplementary strategy for the treatment of liver cancer. Materials and Methods: The purity of amarogentin was assessed by high-performance liquid chromatography. The inhibitory ratios of the liver cell lines were determined using a Cell Counting Kit-8 following treatment with a gradient concentration of amarogentin. Cell apoptosis was detected by flow cytometry using annexin V-fluorescein isothiocyanate/propidium iodide kits. The gene and protein expression of p53-associated molecules, such as Akt, human telomerase reverse transcriptase, RelA, and p38, was detected by real-time quantitative polymerase chain reaction, Western blotting, and immunohistochemical staining in liver cancer cells and mouse tumor tissues after treatment with amarogentin. Results: The inhibitory effect of amarogentin on cell proliferation was more obvious in liver cancer cells, and amarogentin was more likely to induce the apoptosis of liver cancer cells than that of normal liver cells. The gene and protein expression levels of Akt, RelA, and human telomerase reverse transcriptase were markedly higher in the control group than in the preventive group and treatment groups. Only the expression of human telomerase reverse transcriptase was downregulated, accompanied by the upregulation of p53. Conclusion: The results of our study suggest that amarogentin promotes apoptosis of liver cancer cells by the upregulation of p53 and downregulation of human telomerase reverse transcriptase and prevents the malignant transformation of these cells.

miR-644-5p carried by bone mesenchymal stem cell-derived exosomes targets regulation of p53 to inhibit ovarian granulosa cell apoptosis

“…It has been reported that p53 is one of the tumor suppressor proteins that induces tumor cell cycle arrest and regulates programmed apoptosis in cancer cells [27]. Studies have found that Amarogentin can promote the apoptosis of liver cancer cells by up-regulating p53 of cells [28]. Another research points out that the expression of p53 is abnormally up-regulated in human colon cancer cells, and the activation of p53 can induce apoptosis of cancer cells and reduce cell migration [29].…”

Amarogentin Inhibits Liver Cancer Cell Angiogenesis after Insufficient Radiofrequency Ablation via Affecting Stemness and the p53-Dependent VEGFA/Dll4/Notch1 Pathway

“…Amarogentin, an anticancer compound extracted from Swertia davidi Franch , has been reported to inhibit liver cancer, cervical cancer, gastric carcinoma, and skin carcinogenesis in vivo and in vitro [ 11 , 12 , 20 – 22 ]. Sur et al have confirmed that amarogentin significantly reduces the numbers of LCSCs in both the pre- and postinitiation stages of carcinogenesis [ 13 ].…”

“…Then, the cells were cultured at 37°C for 12, 24, and 48 h for subsequent experiments. For amarogentin (21018-84-8, PUSH Bio-Tec, China) treatment, the iRFA models of HepG2 and Huh7 cell lines were incubated in a 50°C water bath for 10 min before treatment with amarogentin (120 μ g/ml) for 24 h. The optimal effective dose of amarogentin for liver cancer cell lines was determined in our previous study [ 12 ].…”

“…Amarogentin, a bioactive molecule extracted from Swertia davidi Franch , has been reported to activate p53 to promote apoptosis in liver cancer cells [ 11 ]. Our previous study has verified that amarogentin prevents the malignant transformation of liver cancer cells through upregulation of p53 [ 12 ]. In addition, amarogentin has been reported to prevent liver carcinogenesis via regulating LCSC renewal [ 13 ].…”

Sensitive quantitative analysis of the bitter glycoside amarogentin by specific monoclonal antibody-based indirect competitive enzyme-linked immunosorbent assay

“…9 More recently, AG was found to induce the apoptosis of liver cancer cells by the upregulation of p53 and downregulation of human telomerase reverse transcriptase. 10 Thus, because the AG content directly reects the potential activity of the extract, the quality control of Gentianaceae through the quantitative analysis of AG has recently attracted much attention. Currently, quantitative analysis for AG has been reported using liquid chromatography-mass spectrometry (LC-MS), 11 high-performance liquid chromatography (HPLC), 11,12 ultra-performance LC-electrospray ionization/MS, 13 and capillary electrophoresis.…”