Abstract
BackgroundGalangin (3,5,7-trihydroxyflavone) is a flavonoid compound found in high concentration in lesser galangal. The objective of this study was to investigate the ability of galangin to inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced the invasion and metastasis of HepG2 liver cancer cells.ResultsFirst, using a cell-matrix adhesion assay, immunofluorescence assay, transwell-chamber invasion/migration assay, and wound healing assay, we observed that galangin exerted an inhibitory effect on TPA-induced cell adhesion, morphology/actin cytoskeleton arrangement, invasion and migration. Furthermore, the results of gelatin zymography and reverse transcriptase polymerase chain reaction (RT-PCR) assays showed that galangin reduced the TPA-induced enzyme activity of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in HepG2 cells; moreover, the messenger RNA level was downregulated. We also observed through a Western blotting assay that galangin strongly inhibited the TPA-induced protein expressions of protein kinase Cα (PKCα), protein kinase Cδ (PKCδ), phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2), the phospho-inhibitor of kappaBα (phospho-IκBα), c-Fos, c-Jun, and nuclear factor kappa B (NF-κB). Next, galangin dose-dependently inhibited the binding ability of NF-κB and activator protein 1 (AP-1) to MMP-2/MMP-9 promoters, respectively, resulting in the suppression of MMP-2/MMP-9 enzyme activity.ConclusionsThe results revealed that galangin effectively inhibited the TPA-induced invasion and migration of HepG2 cells through a protein kinase C/extracellular signal-regulated kinase (PKC/ERK) pathway. Thus, galangin may have widespread applications in clinical therapy as an anti-metastatic medicament.
Highlights
Malignant neoplasm, generally known as cancer, is currently considered one of the most deadly types of diseases
These results demonstrated that treatment with galangin at doses exceeding 5 μM for 24 and 48 h resulted in dose- and timedependent loss of cell viability in HepG2 cells; treatment with doses lower than 5 μM for 24 and 48 h did not cause cytotoxicity
matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) are involved in the inhibition of invasion, motility, and adhesion of cancer cells by galangin; we investigated the inhibitory effect of galangin on TPA-induced matrix metalloproteinases (MMPs)-2/-9 enzyme activity by using gelatin zymography under a condition of serum starvation
Summary
Generally known as cancer, is currently considered one of the most deadly types of diseases. The leading cause of death in patients with cancer is tumour metastasis. Tumour metastasis is a complex process during which cancer cells undergo a series of alterations at intracellular and extracellular levels, including changes that (1) damage intercellular interaction, (2) increase cancer cells and extracellular matrix (ECM) interaction, (3) damage ECM components, and (4) increase the invasion and migration of cancer cells. Metastasis involves the overexpression of proteolytic enzymes, such as matrix metalloproteinases (MMPs) [3]. MMPs are enzymes involved in ECM degradation in physiological processes, such as tissue remodelling and embryonic development. Studies have shown that MMP-2 and MMP-9 are crucial in tumour metastasis, the process of which. The objective of this study was to investigate the ability of galangin to inhibit 12-O-tetradecanoylphorbol13-acetate (TPA)-induced the invasion and metastasis of HepG2 liver cancer cells
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