Abstract
The natural flavonoid chrysin possesses antiproliferative activity against various types of cancers, including hepatocellular carcinoma (HCC), which is a common malignancy. However, the exact mechanism of chrysin antiproliferative activity remains unclear. This research was executed to explore the impact of chrysin on glypican-3 (GPC3)/sulfatase-2 (SULF2) axis and lncRNA-AF085935 expression in HCC using HepG2 cells. Cisplatin (20, 50, 100 μg/mL), chrysin (15, 30, and 60 μg/mL) and the combination of 50 μg/mL cisplatin with different concentrations of chrysin were applied for 24/48 h. Cell viability was determined by MTT assay. Protein levels of GPC3 and SULF2 were measured by ELISA at 24/48 h. GPC3 immunoreactivity was detected by immunocytochemistry. Moreover, GPC3 and SULF2 mRNA expressions in addition to lncRNA-AF085935 expression were assessed by qPCR at 48 h. The GPC3 protein, immunostaining and mRNA levels, SULF2 protein and mRNA levels, as well as lncRNA-AF085935 expression, were decreased significantly with cisplatin and chrysin alone when compared with the control untreated HepG2 cells. However, the combination treatment exhibited a better chemopreventive effect in a dose- and time-dependent manner. This study demonstrated, for the first time, the antiproliferative activity of chrysin against HCC through the suppression of the GPC3/SULF2 axis along with the downregulation of lncRNA-AF085935 expression. Synergistic effect of chrysin with cisplatin could potentiate their antiproliferative action in a dose- and time-dependent manner.
Highlights
Liver cancer is a serious health problem and is considered the world’s main cause of cancer related death
Chrysin Combined with Cisplatin Decreased Glypican-3 (GPC3) Protein and mRNA Expressions in HepG2 Cells
Regarding the statistical analysis of GPC3 immunopositive cells detected by ICC, our results documented that the used sole treatments significantly reduced GPC3 immunostaining in HepG2 cells after 48 h incubation in a concentration-dependent manner when compared with control untreated HepG2 cells, (p < 0.05, Figure 3B,C)
Summary
Liver cancer is a serious health problem and is considered the world’s main cause of cancer related death. The natural polyphenolic compounds that occur in plants were known as flavonoids and possess various beneficial pharmacological actions including anti-inflammatory, antiapoptotic, antioxidants, and anticancer activities [12,13]. Several lncRNAs are dysregulated in liver cancer cells and have been linked to crucial signaling pathways of tumorigenesis. These dysregulated lncRNAs are strongly suggested as novel diagnostic biomarkers and/or therapeutic targets for HCC [32]. This study was carried out to discover a new insight of the antiproliferative action of chrysin alone or with its concurrent treatment with cisplatin against HCC through the impact on the GPC3/SULF2 axis in addition to lncRNA-AF085935 expression
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