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Epigambogic Acid A from Gamboge Stalk Suppresses Non-Small Cell Lung Cancer Progression by Attenuating DIRC1 Expression
Vol 38, Issue 5, 2024
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Abstract
Background: Gamboge, a desiccating resin secreted by the gamboge tree, has shown potential anti-tumor effects. However, its impact and the underlying mechanisms against lung cancer are not well understood. This study explores the molecular mechanisms through which epigambogic acid A, a principal component of gamboge, inhibits the proliferation of non-small cell lung cancer (NSCLC) cells. Methods: Normal lung epithelial cells BEAS-2B and human NSCLC cells were exposed to various concentrations of epigambogic acid A for 48 and 72 hours (h). Cell viability was assessed using a Cell Counting Kit-8 (CCK-8) assay, while colony formation ability was determined through a colony formation assay. Transwell invasion and migration assays were used to evaluate the cells migratory and invasive capacities. Apoptotic processes were analyzed through flow cytometry, and expressions of associated biomarkers were investigated using Western blot. The Illumina HiSeq XTEN platform facilitated sequencing, while quantitative Real-time Polymerase chain reaction (qRT-PCR) quantified the expression of collagen type III alpha 1 chain (COL3A1) and disrupted in renal cancer 1 (DIRC1). Results: Epigambogic acid A significantly inhibited NSCLC cell growth, with a 99.94% inhibition rate. It also reduced cell colony formation and suppressed the migratory and invasive abilities of NSCLC cells, and promoted apoptosis (p < 0.05). Transcriptome sequencing and analysis revealed that epigambogic acid A significantly decreased oncogene levels, including DIRC1 and COL3A1. Furthermore, DIRC1 was found to enhance colony formation and proliferation of NSCLC cells (p < 0.05). Conclusions: This study demonstrates that epigambogic acid A effectively suppresses tumor growth in NSCLC by downregulating DIRC1 expression. These findings suggest that epigambogic acid A is a potential therapeutic target for NSCLC treatment.
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Copyright (c) 2024 Meng Wang, Binxian Jiang, Shuai Li, Kepu Du, Yadan Li, Fei Gao, Mengyu Gao, Bingqing Xu, Zhigang Zhou
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Medical Genetics, University of Torino Medical School, Italy

Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy