Objective: To evaluate the anticancer potential of Cymbopogon citratus extract. Methods: GC-MS analysis was used to identify phytocomponents in the methanolic extract of Cymbopogon citratus. A fractionation method was employed to isolate and assess the bioactivity of different fractions and their cytotoxic activities against cancer cell lines HCT116, LoVo, Caco-2, and HT-29 were investigated. A dual staining method with acridine orange and ethidium bromide was used to assess the effect of the extract on cell apoptosis. Additionally, the expression levels of Bax and TP53 were quantified using realtime PCR in Caco-2 cells treated with the ethyl acetate fraction of Cymbopogon citratus extract. A protein array was employed to profile key pro- and anti-apoptotic proteins in Caco-2 cells. Moreover, molecular docking studies were conducted to investigate the interactions between key compounds of Cymbopogon citratus extract and specific apoptosis-related protein domains (PDB IDs: 7wql and 4bkx). Results: A significant growth inhibition was observed in Caco-2 cells treated with Cymbopogon citratus extract. Among the seven fractions of the plant extract, the ethyl acetate fraction showed the highest cytotoxicity against Caco-2 cells with an IC50 value of (6.16 ± 0.01) μg/mL. The immunofluorescence assay showed that the ethyl acetate fraction could induce apoptosis of Caco-2 cells. Moreover, the fraction upregulated the gene expressions of Bax and TP53 in a dose-dependent manner. The docking analysis demonstrated the interaction of five compounds isolated from the ethyl acetate fraction with key proteins in Caco-2 cells, indicating their anticancer properties. Conclusions: Cymbopogon citratus extract shows anticancer activity against Caco-2 cells by inducing apoptosis. It may be a promising candidate for the treatment of colon cancer, which needs further investigation.
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