Metabolite-Induced Apoptosis by Gundelia tournefortii in A549 Lung Cancer Cells: A Cytotoxic and Gene Expression Study

Gundelia tournefortii代谢物诱导A549肺癌细胞凋亡:细胞毒性和基因表达研究

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作者:Aysun Yuksel ,Damla Nur Celayir ,Ezgi Nurdan Yenilmez Tunoglu ,Lütfi Tutar ,Yusuf Tutar

Abstract

Background/objectives: Gundelia tournefortii (Kenger) is a traditional medicinal plant and exhibits potential anticancer properties. This study investigates the cytotoxic and apoptotic effects of its water extract on human lung carcinoma A549 cells. Methods: A lung cancer cell line was treated with Gundelia tournefortii extract. The metabolic content of the extract that plays key roles in anticancer was detected by high-performance liquid chromatography. Anticancer properties were further detected by a flow cytometer apoptosis assay, and signaling pathways were determined by a PCR array through hub gene expression alteration. Gene enrichment analysis and network pharmacology correlated metabolites and pathways that were involved in anticancer effects. Results: The metabolite content of G. tournefortii was analyzed, and gallic acid, clorogenic acid, hydroxybenzoic acid, caffeic acid, epicatechin, p-coumaric acid, salicylic acid, apigenin 7 glucoside, and cinnamic acid were detected as key compounds. Lung cancer cell line A549 was treated with the extract at increasing concentrations for 24, 48, and 72 h, and its effects on cell viability were determined by MTT analysis. A statistically significant difference was observed for IC50 concentrations depending on incubation times. It was also observed that the G. tournefortii water extract significantly increased apoptosis in A549 cells in comparison with the control group. G. tournefortii extract's effect on lung cancer cell line was measured using the signal pathway PCR array gene set. Gene enrichment analysis of the array expression data confirmed activation of apoptosis-related pathways, particularly the upregulation of BAX and downregulation of HSP90. Conclusions: These findings suggest that G. tournefortii metabolites provide promising selective anticancer drug candidates and potential drug templates to prevent side effects and resistance of current clinical drug treatments. Keywords: Gundelia tournefortii; Tournefort’s gundelia (kenger); apoptosis; array; human lung carcinoma (A549).

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