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Chloroform extract from Sophora Tonkinensis Gagnep. inhibit proliferation, migration, invasion and promote apoptosis of nasopharyngeal carcinoma cells by silencing the PI3K/AKT/mTOR signaling pathway.
- Source :
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Journal of ethnopharmacology [J Ethnopharmacol] 2021 May 10; Vol. 271, pp. 113879. Date of Electronic Publication: 2021 Jan 30. - Publication Year :
- 2021
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Abstract
- Ethnopharmacological Relevance: Sophora Tonkinensis Gagnep. (STG) has been used as a folk medicine for the treatment of different cancers, especially for nasopharyngeal carcinoma, cervical cancer, liver cancer, stomach cancer, lung cancer and leukemia in China. However, the main chemical composition and anticancer mechanism of chloroform extract of STG (CESTG) were still not very clear.<br />Aim of Study: This work was carried out to investigate the anticancer effects and mechanisms of chloroform extract of STG (CESTG) on NPC.<br />Methods: Cultured NPC CNE1, CNE2 and Np69 cells were treated with CESTG. Cells were subjected to cell proliferation, colony-forming, migration and invasion assays. Cell cycle and apoptosis were measured by flow cytometry. Western blotting and morphological analysis were also performed. Tumor xenografts and drug treatments were made in BALB/c nude mice. The main compounds of CESTG was separated by HPLC.<br />Results: CESTG inhibited cell viability, clonal growth and induced cell apoptosis in a dose-dependent manner by silencing the PI3K/AKT/mTOR signaling pathway, which is associated with upregulation of cleaved PARP, caspase 3/7/8/9, cleaved caspase 3/7/8/9, Bax and downregulation of PARP, P-PI3K, PI3K, P-AKT, AKT, P-mTOR, mTOR and Bcl-2. In addition, CESTG arrested cell cycle in the G1/S phase, correlating with decreased levels of cyclin D1/B1, CDK 4 and 6. CESTG decreased cell migration and invasion which correlated with decreased expression of β-catenin, vimentin and snail. CESTG significantly inhibited the tumor growth without toxicity.<br />Conclusion: The results presented here suggest that CESTG could be use as a potential source of NPC therapeutic drug.<br /> (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Antineoplastic Agents therapeutic use
Apoptosis drug effects
Cell Cycle Checkpoints drug effects
Cell Line, Tumor
Cell Movement drug effects
Cell Proliferation drug effects
Cell Survival drug effects
Chloroform chemistry
Female
Humans
Mice, Inbred BALB C
Mice, Nude
Nasopharyngeal Carcinoma metabolism
Nasopharyngeal Neoplasms metabolism
Phosphatidylinositol 3-Kinases metabolism
Plant Extracts chemistry
Plant Extracts therapeutic use
Proto-Oncogene Proteins c-akt metabolism
TOR Serine-Threonine Kinases metabolism
Tumor Stem Cell Assay
Xenograft Model Antitumor Assays
Mice
Antineoplastic Agents pharmacology
Nasopharyngeal Carcinoma drug therapy
Nasopharyngeal Neoplasms drug therapy
Plant Extracts pharmacology
Signal Transduction drug effects
Sophora chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7573
- Volume :
- 271
- Database :
- MEDLINE
- Journal :
- Journal of ethnopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 33524509
- Full Text :
- https://doi.org/10.1016/j.jep.2021.113879