Hepatocellular carcinoma is considered as one of the most serious cancer types. The main objective of this research is to explore Enhalus acoroides (EA) (L.f.) Royle’s cytotoxic effects and methods of action on HepG-2 (hepatocellular carcinoma cell line). For the purpose of identifying the phenolic compounds in EA, high performance liquid chromatography (HPLC) was applied. Using the MTT assay, the anti-proliferative effects on HepG-2 were assessed. The cell cycle arrest and apoptotic processes were investigated using flow cytometry. An analysis was performed to determine how seagrass influenced the mitochondrial membrane potential (ΔψM). The impact of Caspases 3/7 was evaluated using the colorimetric assay. Finally, the expression level of gene expression using quantitative RT-PCR was investigated. The seagrass alcoholic extract effectively and concentration-dependently reduced the growth of HepG-2 cells without inflicting any adverse effects to normal human skin fibroblast HSF. EA primarily triggers apoptosis which results in cell death. A significant decrease in the G0/G1 phase and an increase of cells at S phase were indicators of the S phase cell cycle arrest. The results reflected the depletion in (ΔψM) in HepG-2 dose-dependently. Following therapy for 24 h, caspase 3/7 activities were enhanced. In conclusion, a quantitative real-time RT-PCR investigation for EA seagrass on HepG-2 demonstrated downregulated expression levels of the survival, BCL-2, CDC-2, and CC2DA1 genes. Collectively, the seagrass EA shows great promise as a hepatocellular cancer treatment and possesses the capacity to induce apoptosis in HepG-2.
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